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31.
Initiatedlselected (ISH) and normal (NH) rat hepatocytes were used to study cytoskeleton modifications induced by three liver acting chemicals: 2-AAF, a liver complete carcinogen; PB, a liver tumor promoter; and 4-AAF, a noncarcinogen analogue of 2-AAF. Cytoskeleton alterations were visualized by disappearance of F-actin fibers and tubulin depolymerization. The three drugs induced actin fragmentation in normal hepatocytes; a net loss of actin protein was observed with PB. They also induced varied tubulin depolymerization. The principal difference between chemicals is that 2-AAF led to non-reversible effects, in comparison with PB and 4-AAF which induced reversible damages on cytoskeleton. By contrast to normal hepatocytes, the cytoskeleton of ISH obtained from rats subjected to the resistant hepatocyte protocol was much less susceptible to the effect of the three chemicals. Moreover, we observed a lack of LDH release in the culture medium and a very rapid inducibility of GST activity after exposure of ISH to drugs. The moderate effect of the three chemicals on actin and tubdin in ISH could thus be explained by the resistant metabolic profile of these cells.Abbreviations TPA
12-O-tetradecanoyl-phorbol-13-acetate
- PB
phenobarbital
- 2-AAF
2-acetylaminofluorene
- 4-AAF
4-acetylaminofluorene
- GSH
reduced glutathione
- GST
glutathione-S-transferase
- LDH
lactatedehydrogenase
- NH
normal hepatocytes
- ISH
initiated/selected hepatocytes
- BSA
bovine serum albumin 相似文献
32.
Julie L Richards Johanna R Abend Michelle L Miller Shikha Chakraborty-Sett Stephen Dewhurst Linda E Whetter 《European journal of biochemistry》2003,270(10):2287-2294
CD40 is a receptor with numerous functions in the activation of antigen presenting cells (APCs), particularly dendritic cells (DC). Using phage display technology, we identified linear peptides containing a novel FPGN/S consensus sequence that enhances the binding of phage to a purified murine CD40-immunoglobulin (Ig) fusion protein (CD40-Ig), but not to Ig alone. To examine the ability the FPGN/S peptides to enhance adenoviral infection of CD40-positive cells, we used bifunctional peptides consisting of an FPGN-containing peptide covalently linked to an adenoviral knob-binding peptide (KBP). One of these, FPGN2-KBP, was able to enhance adenoviral infection of both murine and human DCs in a dose-dependent manner. FPGN2-KBP also improved infection of murine B cell blasts, a murine B lymphoma cell line (L10A), and immortalized human B cells. To demonstrate that enhancement of adenoviral infection depended on the presence of CD40, we analyzed infection of the breast cancer line, SKBR3, that does not express CD40 or the adenovirus cellular receptor, CAR. Infection of SKBR3 cells was enhanced by FPGN2-KBP following transient transfection with a plasmid vector that expresses murine CD40, but not when the cells were mock-transfected. In conclusion, we have isolated a peptide that binds to murine CD40, and promotes the uptake of adenoviruses into CD40-expressing cells of both murine and human origin, suggesting that it may have potential applications for antigen delivery to CD40-positive antigen-presenting cells. 相似文献
33.
Karri Silventoinen Sampo Sammalisto Markus Perola Dorret I Boomsma Belinda K Cornes Chayna Davis Leo Dunkel Marlies De Lange Jennifer R Harris Jacob V B Hjelmborg Michelle Luciano Nicholas G Martin Jakob Mortensen Lorenza Nisticò Nancy L Pedersen Axel Skytthe Tim D Spector Maria Antonietta Stazi Gonneke Willemsen Jaakko Kaprio 《Twin research》2003,6(5):399-408
A major component of variation in body height is due to genetic differences, but environmental factors have a substantial contributory effect. In this study we aimed to analyse whether the genetic architecture of body height varies between affluent western societies. We analysed twin data from eight countries comprising 30,111 complete twin pairs by using the univariate genetic model of the Mx statistical package. Body height and zygosity were self-reported in seven populations and measured directly in one population. We found that there was substantial variation in mean body height between countries; body height was least in Italy (177 cm in men and 163 cm in women) and greatest in the Netherlands (184 cm and 171 cm, respectively). In men there was no corresponding variation in heritability of body height, heritability estimates ranging from 0.87 to 0.93 in populations under an additive genes/unique environment (AE) model. Among women the heritability estimates were generally lower than among men with greater variation between countries, ranging from 0.68 to 0.84 when an additive genes/shared environment/unique environment (ACE) model was used. In four populations where an AE model fit equally well or better, heritability ranged from 0.89 to 0.93. This difference between the sexes was mainly due to the effect of the shared environmental component of variance, which appears to be more important among women than among men in our study populations. Our results indicate that, in general, there are only minor differences in the genetic architecture of height between affluent Caucasian populations, especially among men. 相似文献
34.
Benzothiadiazole induces disease resistance in Arabidopsis by activation of the systemic acquired resistance signal transduction pathway 总被引:18,自引:6,他引:12
Kay A. Lawton Leslie Friedrich Michelle Hunt Kris Weymann Terrance Delaney Helmut Kessmann Theodor Staub John Ryals 《The Plant journal : for cell and molecular biology》1996,10(1):71-82
Benzothiadiazole (BTH) is a novel chemical activator of disease resistance in tobacco, wheat and other important agricultural plants. In this report, it is shown that BTH works by activating SAR in Arabidopsis thaliana. BTH-treated plants were resistant to infection by turnip crinkle virus, Pseudomonas syringae pv ‘tomato’ DC3000 and Peronospora parasitica. Chemical treatment induced accumulation of mRNAs from the SAR-associated genes, PR-1, PR-2 and PR-5. BTH treatment induced both PR-1 mRNA accumulation and resistance against P. parasitica in the ethylene response mutants, etr1 and ein2, and in the methyl jasmonate-insensitive mutant, jar1, suggesting that BTH action is independent of these plant hormones. BTH treatment also induced both PR-1 mRNA accumulation and P. parasitica resistance in transgenic Arabidopsis plants expressing the nahG gene, suggesting that BTH action does not require salicylic acid accumulation. However, because BTH-treatment failed to induce either PR-1 mRNA accumulation or P. parasitica resistance in the non-inducible immunity mutant, nim1, it appears that BTH activates the SAR signal transduction pathway. 相似文献
35.
Francisco Berguido Michelle Kagey Charles F. Howard Jr. Susan R. Stapleton 《Primates; journal of primatology》1995,36(3):423-429
Members of the monkey speciesMacaca nigra spontaneously develop impairments in insulin secretion and glucose clearance, and eventually become overtly diabetic. Changes
in certain metabolic signals such as clearance of glucose and insulin increment secreted in an intravenous glucose tolerance
test have allowed the identification of four stages in the progression from non-diabetes to diabetes in monkeys — non-diabetic,
hormonally impaired, borderline diabetic, and diabetic. Recently, another metabolic stage, hyperinsulinemic, was also identified
in these animals. In recent years, other factors besides those listed above have been implicated to be correlated with the
metabolic progression from a nondiabetic to a diabetic state. One of these factors, is insulin like growth factor I (IGF-I).
In diabetic humans who are in poor metabolic control, and in rats with streptozotocin induced ketotic diabetes, serum levels
of IGF-I are lowered by as much as 40–50% of control non-diabetics. If indeed decreased IGF-I levels are correlated with the
onset of diabetes then changes in IGF-I concentrations prior to the clinically diagnosed disease state would be expected.
Using serum samples collected from different animals in a colony ofMacaca nigra in a variety of metabolic states, we have found that IGF-I and insulin levels decrease in each defined metabolic state as
the animals progress from nondiabetic to diabetic. Since IGF-I and insulin levels decrease in a similar fashion in the progression
of this disease then this maybe indicative of the coordinate expression of these two factors. 相似文献
36.
Hydroxyl Radical-Mediated Oxidation of Serotonin: Potential Insights into the Neurotoxicity of Methamphetamine 总被引:1,自引:1,他引:0
Monika Z. Wrona Zhaoliang Yang Michelle McAdams Susan O'Connor-Coates Glenn Dryhurst 《Journal of neurochemistry》1995,64(3):1390-1400
Abstract: When incubated with a hydroxyl radical (HO?)-generating system (ascorbic acid/Fe2+-EDTA/O2/H2O2), 5-hydroxytryptamine (5-HT; serotonin) is rapidly oxidized initially to a mixture of 2,5-, 4,5-, and 5,6-dihydroxytryptamine (DHT). The major reaction product is 2,5-DHT, which at physiological pH exists as its keto tautomer, 5-hydroxy-3-ethylamino-2-oxindole (5-HEO). Rapid autoxidation of 4,5-DHT gives tryptamine-4,5-dione (T-4,5-D), which reacts with the C(3)-centered carbanion of 5-HEO to give 3,3′-bis(2-aminoethyl)-5-hydroxy-[3,7′-bi-1H-indole]-2,4′,5′-3H-trione (7). The latter slowly cyclizes to 3′-(2-aminoethyl)-1′,6′,7′,8′-tetrahydro-5-hydroxyspiro[3H-indole-3,9′-[9H]pyrrolo[2,3-f]quinoline]-2,4′,5′(1H)- trione (9). A minor amount of T-4,5-D dimerizes to give 7,7′-bi-(5-hydroxytryptamine-4-one) (7,7′-D). In the presence of GSH, the reaction of T-4,5-D with 5-HEO is diverted and, in the presence of sufficient concentrations of this tripeptide, completely blocked. This is because GSH preferentially reacts with T-4,5-D to give 7-S-glutathionyltryptamine-4,5-dione (11). The results of this investigation suggest that 5,6-DHT, 5-HEO, 7, and 9 are products unique to the HO?-mediated oxidation of 5-HT. Thus, the observation of other investigators that 5,6-DHT is formed in the brains of rats following a large dose of methamphetamine (MA) suggests that this drug might evoke HO? formation. However, the present in vitro study indicates that 5,6-DHT is a rather minor, unstable product of the HO?-mediated oxidation of 5-HT and suggests that detection of 5-HEO, 7/9, and 11 in rat brain following MA administration could provide additional support for HO? formation. Furthermore, one or more of the intermediates and major products of oxidation of 5-HT by HO? might, in addition to 5,6-DHT, contribute to the MA-induced degeneration of serotonergic neurons. 相似文献
37.
J. D. Penschow Michelle E. Giles John P. Coghlan R. T. Fernley 《Histochemistry and cell biology》1997,107(5):417-422
Carbonic anhydrase VI (CA VI) is a secreted enzyme produced predominantly by serous acinar cells of submandibular and parotid
glands. We have investigated the developmental pattern of CA VI production by these glands in the sheep, from fetal life to
adulthood, using immunohistochemistry. Also, a specific radioimmunoassay for CA VI was used to measure changes in enzyme expression
in the parotid gland postnatally. CA VI is detectable by immunohistochemistry in parotid excretory ducts from 106 days gestation
(term is 145 days), in striated ducts from 138 days and in acinar cells from 1 day postnatal. The duct cell content of CA
VI declined as the acinar cell population increased, a feature also of CA VI immunoreactivity in the submandibular gland.
Production of CA VI by submandibular duct cells was detectable initially at 125 days gestation, and acinar production was
not seen before 29 days post-natal. Apart from the differing ontogeny of CA VI production in ducts and acini of parotid and
submandibular glands, there was a parallel pattern of CA VI expression during the development of these major salivary glands.With
the development of the acinar tissues in the postnatal lamb, there was a dramatic increase (about 600-fold) in the level of
expression of CA VI in the parotid gland between days 7 and 59 as measured by radioimmunoassay.
Accepted: 19 December 1996 相似文献
38.
Expression of Bcl-2 protein in the epiphyseal plate cartilage and trabecular bone of growing rats 总被引:2,自引:0,他引:2
Ying Wang Renée Toury Michelle Hauchecorne N. Balmain 《Histochemistry and cell biology》1997,108(1):45-55
The protooncogene protein, Bcl-2, protects cells from apoptosis and ensures their survival in vitro by inhibiting the action
of the apoptosis-inducer, Bax. Its expression in proliferative and long-lived cells in vivo also indicates that it protects
against cell death. The chondrocytes of the epiphyseal plate cartilage undergo a series of maturation steps and deposit mineral
in the cartilage matrix before dying. The possibility that Bcl-2 helps protect chondrocytes until mineral deposition is completed
was investigated by determining the distribution of Bcl-2 immunoreactivity in the epiphyseal plate cartilage of growing rats
and its subcellular localization, using a specific antibody. The involvement of Bax in the triggering of chondrocyte death
was checked by immunocytochemistry. Bcl-2 expression in the osteoblasts and the final result of their evolution, the osteocytes,
was also examined in trabecular bone. Bcl-2 immunoreactivity was non-uniformly distributed throughout the epiphyseal cartilage.
It was maximal in proliferative chondrocytes, decreased in mature chondrocytes, and low in hypertrophic chondrocytes, whereas
there was Bax immunoreactivity in all chondrocytes examined. Immunolabeling was intense in osteoblasts but considerably lower
in fully differentiated osteocytes. Bcl-2 immunoreactivity was mainly in the cytoplasm of chondrocytes, osteoblasts, and early
osteocytes; the nuclei appeared clear. The subcellular distribution of Bcl-2 immunolabeling in chondrocytes, revealed by gold
particles in the electron microscope, showed that gold particles were frequently concentrated in the mitochondria in all the
cartilage zones and lay mainly within the organelles, not at their periphery. The endoplasmic reticulum contained moderate
immunoreactivity and there were few gold particles in the cytoplasm and nuclei. The number of gold particles decreased in
all the subcellular compartments from proliferative to hypertrophic chondrocytes. In contrast, Bax immunoreactivity changed
little during chondrocyte terminal evolution, and its subcellular distribution mirrored that of Bcl-2. These immunocytochemical
data indicate that Bcl-2 helps maintain chondrocytes and osteoblasts until their terminal maturation.
Accepted: 19 February 1997 相似文献
39.
Ecological correlates of hind-limb length in the Carnivora 总被引:1,自引:0,他引:1
What determines the lengths and proportions of mammalian limbs? While the answer to this question is still largely unknown, a number of workers have recently begun analysing the selection of morphology in a rigorous framework, searching for quantitative links between structure, performance, and their ecological and behavioural context. The present study investigates a variety of ecological and behavioural variables to determine whether or not they are correlated with hind-limb length in the Carnivora. Data were analysed by using phylogenetically independent contrasts and phylogenetic analysis of covariance. We found that traditional perceptions of limb length are often inaccurate; some species widely regarded as relatively long-legged actually have limb lengths near those expected for their body size. Interestingly, relative hind-limb length is not a significant predictor of distance moved daily, home-range area, or prey size. Phylogenetic ANCOVA results, however, indicate a relationship between prey-capture behaviour and relative hind-limb length. These findings suggest that the evolution of carnivoran limb length has been most influenced by selection for prey-capture behaviour. These results, coupled with those of other studies, can be used to suggest which performance variables could most fruitfully be studied in the laboratory to understand the selection of the structure of the mammalian limb. We suggest that relevant performance variables might be: maximum jump height and/or length, the ability to generate outforces, and levels of stress tolerance in limb bones during prey pursuit/capture. 相似文献
40.
Ann-Charlotte E. Granholm Michelle L. Price Michael D. Owen 《Cell and tissue research》1995,280(1):49-57
We have investigated the distribution of tyrosine-hydroxylase-like immunoreactivity in the cerebral ganglia of the American cockroach, Periplaneta americana. Groups of tyrosine-hydroxylase-immunoreactive cell bodies occur in various parts of the three regions of the cerebral ganglia. In the protocerebrum, single large neurons or small groups of neurons are located in the lateral neuropil, adjacent to the calyces, and in the dorsal portion of the pars intercerebralis. Small scattered cell bodies are found in the outer layers of the optic lobe, and clusters of larger cell bodies can be found in the deutocerebrum, medial and lateral to the antennal glomeruli. Thick bundles of tyrosine-hydroxylase-positive nerve fibers traverse the neuropil in the proto- and deutocerebrum and innervate the glomerular and the nonglomerular neuropil with fine varicose terminals. Dense terminal patterns are present in the medulla and lobula of the optic lobe, the pars intercerebralis, the medial tritocerebrum, and the area surrounding the antennal glomeruli, the central body and the mushroom bodies. The pattern of tyrosine-hydroxylase-like immunoreactivity is similar to that previously described for catecholaminergic neurons, but it is distinctly different from the distribution of histaminergic and serotonergic neurons. 相似文献