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1.
Laska M 《Chemical senses》2004,29(2):143-152
The ability of 20 human subjects to distinguish between nine enantiomeric odor pairs sharing an isopropenyl group at the chiral center was tested in a forced-choice triangular test procedure. I found (i). that as a group, the subjects were only able to significantly discriminate the optical isomers of limonene, carvone, dihydrocarvone, dihydrocarveol and dihydrocarvyl acetate, whereas they failed to distinguish between the (+)- and (-)-forms of perillaalcohol, perillaaldehyde, isopulegol and limonene oxide; (ii). marked interindividual differences in discrimination performance, ranging from subjects who were able to significantly discriminate between eight of the nine odor pairs to subjects who failed to do so with six of the nine tasks; and (iii). that with none of the nine odor pairs the antipodes were reported to differ significantly in subjective intensity when presented at equal concentrations. Additional tests of the chemesthetic potency and threshold measurements of the optical isomers of dihydrocarvone, dihydrocarveol, and dihydrocarvyl acetate suggest that the discriminability of these three enantiomeric odor pairs is indeed due to differences in odor quality. Analysis of structure-activity relationships suggest that the combined presence of (i). an isopropenyl group at the chiral center; (ii). a methyl group at the para-position; and/or (iii). an oxygen-containing group at the meta-position allows for the discrimination of enantiomeric odor pairs.  相似文献   

2.
The ability of four squirrel monkeys and three pigtail macaques to distinguish between nine enantiomeric odor pairs sharing an isopropenyl group at the chiral center was investigated in terms of a conditioning paradigm. All animals from both species were able to discriminate between the optical isomers of limonene, carvone, dihydrocarvone, dihydrocarveole and dihydrocarvyl acetate, whereas they failed to distinguish between the (+)- and (-)-forms of perillaaldehyde and limonene oxide. The pigtail macaques, but not the squirrel monkeys, also discriminated between the antipodes of perillaalcohol and isopulegol. A comparison of the across-task patterns of discrimination performance shows a high degree of similarity among the two primate species and also between these nonhuman primates and human subjects tested in an earlier study on the same tasks. These findings suggest that between-species comparisons of the relative size of olfactory brain structures or of the number of functional olfactory receptor genes are poor predictors of olfactory discrimination performance with enantiomers.  相似文献   

3.
M Laska  P Teubner 《Chemical senses》1999,24(2):161-170
We tested the ability of human subjects to distinguish between enantiomers, i.e. odorants which are identical except for chirality. In a forced-choice triangular test procedure 20 subjects were repeatedly presented with 10 enantiomeric odor pairs and asked to identify the bottle containing the odd stimulus. We found (i) that as a group, the subjects were only able to significantly discriminate the optical isomers of alpha-pinene, carvone and limonene, whereas they failed to distinguish between the (+)- and (-)-forms of menthol, fenchone, rose oxide, camphor, alpha-terpineol, beta-citronellol and 2-butanol; (ii) marked individual differences in discrimination performance, ranging from subjects who were able to significantly discriminate between 6 of the 10 odor pairs to subjects who failed to do so with 9 of the 10 tasks; (iii) that with none of the 10 odor pairs were the antipodes reported to differ significantly in subjective intensity when presented at equal concentrations; and (iv) that error rates were quite stable and did not differ significantly between sessions, and thus, we observed a lack of learning or training effects. Additional tests of the degree of trigeminality and threshold measurements of the optical isomers of alpha-pinene, carvone and limonene suggest that the discriminability of these three enantiomeric odor pairs is indeed due to differences in odor quality. These findings support the assumption that enantioselective molecular odor receptors may only exist for some but not all volatile enantiomers and thus that chiral recognition of odorants may not be a general phenomenon but is restricted to some substances.  相似文献   

4.
In the present study, we examined the concentration dependenceof odor discrimination in turtle olfactory bulbar responsesusing the cross-adaptation technique. In the odorant pairs withdiverse molecular structures, the degree of discrimination wasunchanged or only slightly decreased with an increase in odorantconcentrations, suggesting that odorants are well discriminatedeven at high concentrations. In the odorant pairs with closelyrelated molecular structures, the degree of discrimination wasdecreased with an increase in odorant concentrations. An increasein the temperature of turtle olfactory epithelium also decreasedthe ability to discriminate these odorants. There was a goodcorrelation between changes in the odor discriminating abilityinduced by an increase in odor concentrations and those inducedby a temperature increase. The liposomes were made of lipidsextracted from the turtle olfactory epithelia and changes oftheir membrane fluidity induced by adsorption of odorants weremonitored with DPH. There was a good correlation between a decreasein odor discriminating ability and the membrane fluidity changesinduced by odorants. We suggest that decreases in odor discriminatingability induced either by an increase in odor concentrationor by a temperature increase are ultimately caused by changesin the membrane fluidity. Chem. Senses 22: 553–563, 1997.  相似文献   

5.
Social relationships in domestic fowl are commonly assumed to rely on social recognition and its pre-requisite, discrimination of group-mates. If this is true, then the unnatural physical and social environments in which commercial laying hens are typically housed, when compared with those in which their progenitor species evolved, may compromise social function with consequent implications for welfare. Our aims were to determine whether adult hens can discriminate between unique pairs of familiar conspecifics, and to establish the most appropriate method for assessing this social discrimination. We investigated group-mate discrimination using two learning tasks in which there was bi-directional exchange of visual, auditory and olfactory information. Learning occurred in a Y-maze task (p < 0.003; n = 7/8) but not in an operant key-pecking task (p = 0.001; n = 1/10). A further experiment with the operant-trained hens examined whether failure was specific to the group-mate social discrimination or to the response task. Learning also failed to occur in this familiar/unfamiliar social discrimination task (p = 0.001; n = 1/10). Our findings demonstrate unequivocally that adult laying hens kept in small groups, under environmental conditions more consistent with those in which sensory capacities evolved, can discriminate group members: however, appropriate methods to demonstrate discrimination are crucial.  相似文献   

6.
Yee  KK; Costanzo  RM 《Chemical senses》1998,23(5):513-519
Following recovery from olfactory nerve transection, animals regain their ability to discriminate between odors. Odor discrimination is restored after new neurons establish connections with the olfactory bulb. However, it is not known if the new connections alter odor quality perception. To address this question, 20 adult hamsters were first trained to discriminate between cinnamon and strawberry odors. After reaching criterion (> or = 90% correct response), half of the animals received a bilateral nerve transection (BTX) and half a surgical sham procedure. Animals were not tested again until day 40, a point in recovery when connections are re-established with the bulb. When BTX animals were tested without food reinforcement, they could not perform the odor discrimination task. Sham animals, however, could discriminate, demonstrating that the behavioral response had not been extinguished during the 40 day period. When reinforcement was resumed, BTX animals were able to discriminate between cinnamon and strawberry after four test sessions. In addition, their ability to discriminate between these two familiar odors was no different than that of BTX and sham animals tested with two novel odors, baby powder and coffee. These findings suggest that, after recovery from nerve transection, there are alterations in sensory perception and that restoration of odor quality discrimination requires that the animal must again learn to associate individual odor sensations with a behavioral response.   相似文献   

7.
Subclinical hypothyroidism has been accused for coronary heart disease, lipid metabolism disorders, neuropsychiatric disorders, infertility or pregnancy related problems with various strength of evidence. Currently there is insufficient knowledge about olfaction and taste functions in subclinical hypothyroidism. Aim of the present study is to investigate the degree of smell and taste dysfunction in patients with subclinical hypothyroidism. 28 subclinical hypothyroid patients, and 31 controls enrolled in the prospective study in Istanbul, Turkey. Subclinical hypothyroid patients were treated with L-thyroxine for 3 months. Psychophysiological olfactory testing was performed using odor dispensers similar to felt-tip pens (“Sniffin’ Sticks”, Burghart, Wedel, Germany). Taste function tests were made using "Taste Strips" (Burghart, Wedel, Germany) which are basically tastant adsorbed filter paper strip. Patients scored lower on psychophysical olfactory tests than controls (odor thresholds:8.1±1.0 vs 8.9±1.1, p = 0.007; odor discrimination:12.4±1.3 vs 13.1±0.9, p = 0.016; odor identification:13.1±0.9 vs 14.0±1.1, p = 0.001; TDI score: 33.8±2.4 vs 36.9±2.1, p = 0.001). In contrast, results from psychophysical gustatory tests showed only a decreased score for “bitter” in patients, but not for other tastes (5.9±1.8 vs 6.6±1.0, p = 0.045). Three month after onset of treatment olfactory test scores already indicated improvement (odor thresholds:8.1±1.0 vs 8.6±0.6, p<0.001; odor discrimination:12.4±1.31 vs 12.9±0.8, p = 0.011; odor identification:13.1±0.9 vs 13.9±0.8, p<0.001; TDI scores:33.8±2.4 vs 35.5±1.7, p<0.001) respectively. Taste functions did not differ between groups for sweet, salty and, sour tastes but bitter taste was improved after 3 months of thyroxin substitution (patients:5.9±1.8 vs 6.6±1.2, p = 0.045). Correlation of changes in smell and taste, with thyroid function test were also evaluated. TSH, fT4 were found have no correlation with smell and taste changes with treatment. However bitter taste found positively correlated with T3 with treatment(r: 0.445, p: 0.018). Subclinical hypothyroid patients exhibited a significantly decreased olfactory sensitivity; in addition, bitter taste was significantly affected. Most importantly, these deficits can be remedied on average within 3 months with adequate treatment.  相似文献   

8.
Laska M 《Chemical senses》2005,30(9):755-760
The ability of human subjects to distinguish between aliphatic C6 alcohols differing in presence, position, or configuration (i.e., cis-trans geometry) of a double bond was tested. In a forced-choice triangular test procedure, 20 subjects were repeatedly presented with all 21 binary combinations of the seven stimuli and asked to identify the bottle containing the odd stimulus. I found (a) that as a group, the subjects performed significantly above chance level in all tasks but two and thus were clearly able to discriminate between most of the odor pairs presented; (b) marked interindividual differences in discrimination performance, ranging from subjects who were able to significantly distinguish between all 21 odor pairs to subjects who failed to do so with 10 of the tasks; (c) that odor pairs involving two hexenols were significantly more difficult to discriminate than odor pairs that involved hexanol and one of the hexenols; (d) that odor pairs involving hexenols sharing the same geometry but differing in the position of the double bond by only one carbon atom were significantly more difficult to distinguish than odor pairs that involved hexenols differing by two carbon atoms; (e) that odor pairs involving 4-hexenols were significantly easier to discriminate than 3-hexenols, which, in turn, were significantly easier to distinguish than 2-hexenols; and (f) that odor pairs involving two cis-hexenols were significantly more difficult to discriminate than odor pairs that involved two trans-hexenols. These findings demonstrate that the presence as well as the position and configuration of a double bond affected discriminability in a systematic manner and suggest that these molecular structural features may be important determinants of the interaction between stimulus molecule and olfactory receptor and thus may affect odor quality of aliphatic alcohols.  相似文献   

9.

Background

Timely decision making is crucial for survival and reproduction. Organisms often face a speed-accuracy trade-off, as fully informed, accurate decisions require time-consuming gathering and treatment of information. Optimal strategies for decision-making should therefore vary depending on the context. In mammals, there is mounting evidence that multiple systems of perceptual discrimination based on different neural circuits emphasize either fast responses or accurate treatment of stimuli depending on the context.

Methodology/Principal Findings

We used the ant Camponotus aethiops to test the prediction that fast information processing achieved through direct neural pathways should be favored in situations where quick reactions are adaptive. Social insects discriminate readily between harmless group-members and dangerous strangers using easily accessible cuticular hydrocarbons as nestmate recognition cues. We show that i) tethered ants display rapid aggressive reactions upon presentation of non-nestmate odor (120 to 160 ms); ii) ants'' aggressiveness towards non-nestmates can be specifically reduced by exposure to non-nestmate odor only, showing that social interactions are not required to alter responses towards non-nestmates; iii) decision-making by ants does not require information transfer between brain hemispheres, but relies on side-specific decision rules.

Conclusions/Significance

Our results strongly suggest that first-order olfactory processing centers (up to the antennal lobes) are likely to play a key role in ant nestmate recognition. We hypothesize that the coarse level of discrimination achieved in the antennal lobes early in odor processing provides enough information to determine appropriate behavioral responses towards non-nestmates. This asks for a reappraisal of the mechanisms underlying social recognition in insects.  相似文献   

10.
Impaired olfaction is an early pre-motor symptom of Parkinson''s disease. The neuropathology underlying olfactory dysfunction in Parkinson''s disease is unknown, however α-synuclein accumulation/aggregation and altered neurogenesis might play a role. We characterized olfactory deficits in a transgenic mouse model of Parkinson''s disease expressing human wild-type α-synuclein under the control of the mouse α-synuclein promoter. Preliminary clinical observations suggest that rasagiline, a monoamine oxidase-B inhibitor, improves olfaction in Parkinson''s disease. We therefore examined whether rasagiline ameliorates olfactory deficits in this Parkinson''s disease model and investigated the role of olfactory bulb neurogenesis. α-Synuclein mice were progressively impaired in their ability to detect odors, to discriminate between odors, and exhibited alterations in short-term olfactory memory. Rasagiline treatment rescued odor detection and odor discrimination abilities. However, rasagiline did not affect short-term olfactory memory. Finally, olfactory changes were not coupled to alterations in olfactory bulb neurogenesis. We conclude that rasagiline reverses select olfactory deficits in a transgenic mouse model of Parkinson''s disease. The findings correlate with preliminary clinical observations suggesting that rasagiline ameliorates olfactory deficits in Parkinson''s disease.  相似文献   

11.
We tested the ability of human subjects to distinguish between aliphatic odorants sharing the same number of carbon atoms but differing in their functional groups. 1-Alcohols, n-aldehydes, 2-ketones and n-carboxylic acids of four, six and eight carbon atoms, respectively, were employed. In a forced-choice triangular test procedure 20 subjects were repeatedly presented with 18 odor pairs and asked to identify the bottle containing the odd stimulus. We found (i) that as a group, the subjects performed significantly above chance level in all tasks and thus were clearly able to discriminate between all odor pairs presented; (ii) marked interindividual differences in discrimination performance, ranging from subjects who were able to significantly distinguish between all 18 odor pairs to subjects who failed to do so with 1/3 of the tasks; (iii) a lack of significant differences in performance between male and female, and between Japanese and German subjects; (iv) that odor pairs that involved 2-ketones and/or n-carboxylic acids were significantly easier to discriminate compared to odor pairs that involved 1-alcohols and/or n-aldehydes, and thus a clear dependence of discriminability on type of functional group; and (v) that aliphatic odorants with eight carbon atoms (irrespective of their oxygen moiety) were significantly more difficult to discriminate from each other compared to substances with four or six carbon atoms. The results suggest that functional groups may be an important determinant of the interaction between stimulus molecule and olfactory receptor in aliphatic substances, and thus may be a molecular property affecting odor quality in a substance class-specific manner.  相似文献   

12.
Summary The work reported here is motivated by questions relating to the perception of olfactory cues in the discrimination of nestmates and kin in the honeybeeApis mellifera. Two sets of experiments are discussed. The first deals with the perception of individual compounds in mixtures made up from various pairs of volatile (citral, geraniol, linalool, and limonene) and nonvolatile (un- and dodecanoic acids) compounds. The second deals with the ability of worker honeybees to discriminate between mixtures made up from the same two compounds (un- and dodecanoic acids; tri- and pentacosane) combined in different proportions. All experiments employ differential conditioning of the proboscis extension reflex as an assay of the ability of workers to discriminate between two odors. Results show that workers can relate mixtures to their component parts, and that workers can discriminate between mixtures of two very similar compounds as long as the proportions are relatively dissimilar.  相似文献   

13.
The Drosophila larva possesses just 21 unique and identifiable pairs of olfactory sensory neurons (OSNs), enabling investigation of the contribution of individual OSN classes to the peripheral olfactory code. We combined electrophysiological and computational modeling to explore the nature of the peripheral olfactory code in situ. We recorded firing responses of 19/21 OSNs to a panel of 19 odors. This was achieved by creating larvae expressing just one functioning class of odorant receptor, and hence OSN. Odor response profiles of each OSN class were highly specific and unique. However many OSN-odor pairs yielded variable responses, some of which were statistically indistinguishable from background activity. We used these electrophysiological data, incorporating both responses and spontaneous firing activity, to develop a bayesian decoding model of olfactory processing. The model was able to accurately predict odor identity from raw OSN responses; prediction accuracy ranged from 12%-77% (mean for all odors 45.2%) but was always significantly above chance (5.6%). However, there was no correlation between prediction accuracy for a given odor and the strength of responses of wild-type larvae to the same odor in a behavioral assay. We also used the model to predict the ability of the code to discriminate between pairs of odors. Some of these predictions were supported in a behavioral discrimination (masking) assay but others were not. We conclude that our model of the peripheral code represents basic features of odor detection and discrimination, yielding insights into the information available to higher processing structures in the brain.  相似文献   

14.
Most competition studies between species are conducted from a population-level approach. Few studies have examined inter-specific competition in conjunction with intra-specific competition, with an individual-based approach. To our knowledge, none has been conducted on marine top predators. Sympatric Galapagos fur seals (Arctocephalus galapagoensis) and sea lions (Zalophus wollebaeki) share similar geographic habitats and potentially compete. We studied their foraging niche overlap at Cabo Douglas, Fernandina Island from simultaneously collected dive and movement data to examine spatial and temporal inter- and intra-specific competition. Sea lions exhibited 3 foraging strategies (shallow, intermediate and deep) indicating intra-specific competition. Fur seals exhibited one foraging strategy, diving predominantly at night, between 0–80 m depth and mostly at 19–22 h. Most sea lion dives also occurred at night (63%), between 0–40 m, within fur seals'' diving depth range. 34% of sea lions night dives occurred at 19–22 h, when fur seals dived the most, but most of them occurred at dawn and dusk, when fur seals exhibited the least amount of dives. Fur seals and sea lions foraging behavior overlapped at 19 and 21 h between 0–30 m depths. Sea lions from the deep diving strategy exhibited the greatest foraging overlap with fur seals, in time (19 h), depth during overlapping time (21–24 m), and foraging range (37.7%). Fur seals foraging range was larger. Cabo Douglas northwest coastal area, region of highest diving density, is a foraging “hot spot” for both species. Fur seals and sea lions foraging niche overlap occurred, but segregation also occurred; fur seals primarily dived at night, while sea lions exhibited night and day diving. Both species exploited depths and areas exclusive to their species. Niche breadth generally increases with environmental uncertainty and decreased productivity. Potential competition between these species could be greater during warmer periods when prey availability is reduced.  相似文献   

15.
Using a behavioral paradigm designed to simulate olfactory-guidedforaging, the ability of five squirrel monkeys to distinguishiso-amyl acetate from n-and iso-forms of other acetic esters(ethyl acetate to decyl acetate) and from other esters carryingthe iso-amyl group (iso-amyl propionate to iso-amyl capronate)was investigated. We found (i) that all five animals were clearlyable to discriminate between all odor pairs tested; (ii) a significantnegative correlation between discrimination performance andstructural similarity of odorants in terms of differences incarbon chain length of both the aliphatic alcohol group andthe aliphatic acid group of the esters; and (iii) that iso-and n-amyl acetate were perceived as qualitatively similar despitedifferent steric conformation. Using a triple-forced choiceprocedure, 20 human subjects were tested on the same tasks inparallel and showed a very similar pattern of discriminationperformance compared with the squirrel monkeys. Thus, the resultsof this study provide evidence of well-developed olfactory discriminationability in squirrel monkeys for aliphatic esters and supportthe assumption that human and non-human primates may share commonprinciples of odor quality perception. Chem. Senses 22: 457–465,1997.  相似文献   

16.
Diving behaviour was investigated in female subantarctic fur seals (Arctocephalus tropicalis) breeding on Amsterdam Island, Indian Ocean. Data were collected using electronic Time Depth Recorders on 19 seals during their first foraging trip after parturition in December, foraging trips later in summer, and during winter. Subantarctic fur seals at Amsterdam Island are nocturnal, shallow divers. Ninety-nine percent of recorded dives occurred at night. The diel dive pattern and changes in dive parameters throughout the night suggest that fur seals follow the nycthemeral migrations of their main prey. Seasonal changes in diving behaviour amounted to the fur seals performing progressively deeper and longer dives from their first foraging trip through winter. Dive depth and dive duration increased from the first trip after parturition (16.6 ± 0.5 m and 62.1 ± 1.6 s respectively, n=1000) to summer (19.0 ± 0.4 m and 65 ± 1 s, respectively, n=2000) through winter (29.0 ± 1.0 m and 91.2 ± 2.2 s, respectively, n=800). In summer, subantarctic fur seals increased the proportion of time spent at the bottom during dives of between 10 and 20 m, apparently searching for prey when descending to these depths, which corresponded to the oceanic mixed layer. In winter, fur seals behaved similarly when diving between 20 and 50 m, suggesting that the most profitable depths for feeding moved down during the study period. Most of the dives did not exceed the physiological limits of individuals. Although dive frequency did not vary (10 dives/h of night), the vertical travel distance and the time spent diving increased throughout the study period, while the post-dive interval decreased, indicating that subantarctic fur seals showed a greater diving effort in winter, compared to earlier seasons. Accepted: 1 August 1999  相似文献   

17.
Olfactory systems combine an extraordinary molecular sensitivity with robust synaptic plasticity. Central neuronal circuits that perform pattern recognition in olfaction typically discriminate between hundreds of molecular species and form associations between odor onsets and behavioral contingencies that can last a lifetime. Two design features in the olfactory system of the terrestrial mollusk Limax maximus may be common elements of olfactory systems that display the twin features of broad molecular sensitivity and rapid odor learning: spatially coherent oscillations in the second-order circuitry that receives sensory input; and involvement of the interneuronal messengers nitric oxide (NO) and carbon monoxide (CO) in sensory responses and circuit dynamics of the oscillating olfactory network. The principal odor processing center in Limax, the procerebrum (PC) of the cerebral ganglion, contains on the order of 105 local interneurons and receives both direct and processed input from olfactory receptors. Field potential recordings in the PC show an oscillation at approximately 0.7 Hz that is altered by odor input. Optical recordings of voltage changes in local regions of the PC show waves of depolarization that originate at the distal pole and propagate to the base of the PC. Weak odor stimulation transiently switches PC activity from a propagating mode to a spatially uniform mode. The field potential oscillation in the PC lobe depends on intercellular communication via NO, based on opposing effects of reagents that decrease or increase NO levels in the PC. Inhibition of NO synthase slows the field potential oscillation, while application of exogenous NO increases the oscillation frequency. A role for CO in PC dynamics is suggested by experiments in which CO liberation increases the PC oscillation frequency. These design features of the Limax PC lobe odor processing circuitry may relate to synaptic plasticity that subserves both connection of new receptors throughout the life of the slug and its highly developed odor learning ability. © 1996 John Wiley & Sons, Inc.  相似文献   

18.
Conditioned honeybee workers can discriminate between enantiomeric pairs which are both congruous and incongruous odorants for human beings. These results are discussed in terms of appropriately chiral chemoreceptors, which would enable honeybee workers to distinguish floral odor sources that differ only in enantiomeric identity.  相似文献   

19.
Molecular and cellular studies have begun to unravel a neurobiological basis of olfactory processing, which appears conserved among vertebrate and invertebrate species. Studies have shown clearly that experience-dependent coding of odor identity occurs in “associative” olfactory centers (the piriform cortex in mammals and the mushroom body [MB] in insects). What remains unclear, however, is whether associative centers also mediate innate (spontaneous) odor discrimination and how ongoing experience modifies odor discrimination. Here we show in naïve flies that Gαq-mediated signaling in MB modulates spontaneous discrimination of odor identity but not odor intensity (concentration). In contrast, experience-dependent modification (conditioning) of both odor identity and intensity occurs in MB exclusively via Gαs-mediated signaling. Our data suggest that spontaneous responses to odor identity and odor intensity discrimination are segregated at the MB level, and neural activity from MB further modulates olfactory processing by experience-independent Gαq-dependent encoding of odor identity and by experience-induced Gαs-dependent encoding of odor intensity and identity.  相似文献   

20.
‘Sniffin’ Sticks' is a new test of nasal chemosensoryperformance based on pen-like odor dispensing devices. It comprisesthree tests of olfactory function, namely tests for odor threshold(n-butanol, testing by means of a single staircase), odor discrimination(15 pairs of odorants, triple forced choice) and odor identification(16 common odorants, multiple forced choice from four verbalitems per test odorant). After extensive preliminary investigationsthe tests were applied to a group of 104 healthy volunteers(52 female, 52 male, mean age 49.5 years, range 18–84years) in order to establish test-retest reliability and tocompare them with an established measure of olfactory performance(the Connecticut Chemosensory Clinical Research Center Test,CCCRC). Performance decreased with increasing age of the subjects(  相似文献   

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