全文获取类型
收费全文 | 1275篇 |
免费 | 155篇 |
出版年
2022年 | 11篇 |
2021年 | 17篇 |
2020年 | 15篇 |
2019年 | 14篇 |
2018年 | 21篇 |
2017年 | 19篇 |
2016年 | 29篇 |
2015年 | 41篇 |
2014年 | 65篇 |
2013年 | 59篇 |
2012年 | 84篇 |
2011年 | 79篇 |
2010年 | 46篇 |
2009年 | 47篇 |
2008年 | 73篇 |
2007年 | 57篇 |
2006年 | 50篇 |
2005年 | 56篇 |
2004年 | 53篇 |
2003年 | 50篇 |
2002年 | 50篇 |
2001年 | 34篇 |
2000年 | 36篇 |
1999年 | 33篇 |
1998年 | 25篇 |
1997年 | 17篇 |
1996年 | 13篇 |
1995年 | 10篇 |
1994年 | 9篇 |
1993年 | 12篇 |
1992年 | 27篇 |
1991年 | 19篇 |
1990年 | 34篇 |
1989年 | 29篇 |
1988年 | 20篇 |
1987年 | 11篇 |
1986年 | 21篇 |
1985年 | 15篇 |
1984年 | 18篇 |
1983年 | 13篇 |
1982年 | 9篇 |
1981年 | 7篇 |
1980年 | 8篇 |
1979年 | 12篇 |
1978年 | 10篇 |
1977年 | 6篇 |
1976年 | 9篇 |
1975年 | 5篇 |
1974年 | 5篇 |
1973年 | 6篇 |
排序方式: 共有1430条查询结果,搜索用时 46 毫秒
21.
Motor units in the cat diaphragm (DIA) were isolated in situ by microdissection and stimulation of C5 ventral root filaments. Motor units were classified based on their isometric contractile force responses and fatigue indexes (FI). The muscle fibers belonging to individual units (i.e., the muscle unit) were identified using the glycogen-depletion method. Fibers were classified as type I or II based on histochemical staining for myofibrillar adenosine triphosphatase (ATPase) after alkaline preincubation. The rate of succinate dehydrogenase (SDH) activity of each fiber was determined using a microphotometric procedure. The location of capillaries was determined from muscle cross sections stained for ATPase after acid (pH = 4.2) preincubation. The capillarity of muscle unit fibers was determined by counting the number of capillaries surrounding fibers and by calculating the number of capillaries per fiber area. A significant correlation was found between the fatigue resistance of DIA units and the mean SDH activity of muscle unit fibers. A significant correlation was also observed between DIA unit fatigue resistance and both indexes of muscle unit fiber capillarity. The mean SDH activity and mean capillary density of muscle unit fibers were also correlated. We conclude that DIA motor unit fatigue resistance depends, at least in part, on the oxidative capacity and capillary density of muscle unit fibers. 相似文献
22.
Physical mapping of the von Recklinghausen neurofibromatosis region on chromosome 17 总被引:15,自引:9,他引:6
下载免费PDF全文
![点击此处可从《American journal of human genetics》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Jane W. Fountain Margaret R. Wallace Anne M. Brereton Peter O''''Connell Raymond L. White Donna C. Rich David H. Ledbetter Robin J. Leach R. E. Keith Fournier Anil G. Menon James F. Gusella David Barker Karen Stephens Francis S. Collins 《American journal of human genetics》1989,44(1):58-67
The von Recklinghausen neurofibromatosis (NF1) locus has been linked to chromosome 17, and recent linkage analyses place the gene on the proximal long arm. NF1 probably resides in 17q11.2, since two unrelated NF1 patients have been identified who possess constitutional reciprocal translocations involving 17q11.2 with chromosomes 1 and 22. We have used a somatic-cell hybrid from the t(17;22) individual, along with other hybrid cell lines, to order probes around the NF1 locus. An additional probe, 17L1, has been isolated from a NotI linking library made from flow-sorted chromosome 17 material and has been mapped to a region immediately proximal to the translocation breakpoint. While neither NF1 translocation breakpoint has yet been identified by pulse-field gel analysis, an overlap between two probes, EW206 and EW207, has been detected. Furthermore, we have identified the breakpoint in a non-NF1 translocation, SP-3, on the proximal side of the NF1 locus. This breakpoint has been helpful in creating a 1,000-kb pulsed-field map, which includes the closely linked NF1 probes HHH202 and TH17.19. The combined somatic-cell hybrid and pulsed-field gel analysis we report here favors the probe order D17Z1-HHH202-TH17.19-CRYB1-17L1-NF1- (EW206, EW207, EW203, L581, L946)-(ERBB2, ERBA1). The agreement in probe ordering between linkage analysis and physical mapping is excellent, and the availability of translocation breakpoints in NF1 should now greatly assist the cloning of this locus. 相似文献
23.
A cyclic AMP response element mediates repression of tyrosine aminotransferase gene transcription by the tissue-specific extinguisher locus Tse-1 总被引:30,自引:0,他引:30
Tyrosine aminotransferase (TAT) gene expression is liver specific and inducible by glucocorticoids and via the cAMP signaling pathway. In fibroblasts and other nonliver cells the gene is subject to negative control by the trans-dominant tissue-specific extinguisher locus Tse-1. We identified a hepatocyte-specific enhancer that is repressed by Tse-1. Two distinct sequence motifs are absolutely essential for function of this enhancer: a cAMP response element (CRE), which is the target for repression by Tse-1, and a hepatocyte-specific element. The specificity of the enhancer is generated by the combination of these two essential elements, which are fully interdependent. In vivo footprinting indicates that Tse-1 acts by affecting protein binding at the CRE. A direct antagonism between Tse-1 and the cAMP signaling pathway suggests that Tse-1 plays a role in control of developmental activation of the TAT gene. 相似文献
24.
Selection of field populations originating from several countries allowed us to isolate 13 strains ofDrosophila melanogaster resistant to parathion.In vitro studies of acetylcholinesterase inhibition by paraoxon have been carried out on purified enzymes: most of the resistant strains harbor an altered acetylcholinesterase. Enzymes with higher resistance levels have been characterized with respect to their cross-resistance toward several insecticides. The patterns obtained have permitted us to group them and to delineate four categories. The existence of four distinct types of protein suggests that several mutations of acetylcholinesterase are responsible for insecticide resistance inDrosophila. 相似文献
25.
The synthesis of a variety of important biochemicals involves multistep enzyme-catalyzed reactions. In many cases, the optimal operating pH is much different for the individual enzymatic steps of such synthesis reactions. Yet, it may be beneficial if such reaction steps are combined or paired, allowing them to occur simultaneously, in proximity to one another, and at their respective optimal pH. This can be achieved by separating the micro-environments of the two steps of a reaction pathway using a thin urease layer that catalyzes an ammonia-forming reaction. In this article, the pH control system in a commercial immobilized glucose (xylose) isomerase pellet, which has an optimal pH of 7.5, is demonstrated. This system allows the glucose isomerase to have near its optimal pH activity when immersed in a bulk solution of pH 4.6. A theoretical analysis is also given for the effective fraction of the immobilized glucose isomerase, which remains active when the bulk pH is at 4.6 in the presence of 20 mM urea versus when the bulk pH is at its optimal pH of 7.5. Both theoretical and experimental results show that this pH control system works well in this case. (c) 1996 John Wiley & Sons, Inc. 相似文献
26.
Drosophila melanogaster acetylcholinesterase: Identification and expression of two mutations responsible for cold- and heat-sensitive phenotypes 总被引:2,自引:0,他引:2
Annick Mutero Jean-Marc Bride Madeleine Pralavorio Didier Fournier 《Molecular & general genetics : MGG》1994,243(6):699-705
Ace
IJ29 and Ac
IJ40 are cold- and heat-sensitive variants of the gene coding for acetylcholinesterase in Drosophila melanogaster. In the homozygous condition, these mutations are lethal when animals are raised at restrictive temperatures, i.e., below 23° C for Ace
IJ29 or above 25° C for Ace
IJ40. The coding regions of the gene in these mutants were sequenced and mutations changing Ser374 to Phe in Ace
IJ29 and Pro75 to Leu in Ace
IJ40 were found. Acetylcholinesterases bearing these mutations were expressed in Xenopus oocytes and we found that these mutations decrease the secretion rate of the protein most probably by affecting its folding. This phenomenon is exacerbated at restrictive temperatures decreasing the amount of secreted acetylcholinesterase below the lethality threshold. In parallel, the substitution of the conserved Asp248 by an Asn residue completely inhibits the activity of the enzyme and its secretion, preventing the correct folding of the protein in a non-conditional manner. 相似文献
27.
Claude Bouchard Angelo Tremblay Jean-Pierre Desprs Germain Thriault Andr Nadeauf Paul J. Lupien Sital Moorjani Denis Prudhomme Guy Fournier 《Obesity (Silver Spring, Md.)》1994,2(5):400-410
Seven pairs of young adult male identical twins completed a negative energy balance protocol during which they exercised on cycle ergometers twice a day, 9 out of 10 days, over a period of 93 days while being kept on a constant daily energy and nutrient intake. The total energy deficit caused by exercise above the estimated energy cost of body weight maintenance reached 244 ± 9.8 MJ (Mean ± SEM). Baseline energy intake was estimated over a period of 17 days preceding the negative energy balance protocol. Mean body weight loss was 5.0 kg (SEM = 0.6) (p <0.001) and it was entirely accounted for by the loss of fat mass (p <0.001). Fat-free mass was unchanged. Body energy losses reached 191 MJ (SEM = 24) (p <0.001) which represented about 78% of the estimated energy deficit. Subcutaneous fat loss was slightly more pronounced on the trunk than on the limbs as estimated from skinfolds, circumferences, and computed tomography (CT). The reduction in CT-assessed abdominal visceral fat was quite striking, from 81 cm2 (SEM = 5) to 52 cm2 (SEM = 6) (p <0.001). At the same submaximal power output level, subjects oxidized more lipids than carbohydrates after the program as indicated by the changes in the respiratory exchange ratio (p <0.05). Intrapair resemblance was observed for the changes in body weight (p <0.05), fat mass (P <0.01), percent fat (p <0.01), body energy content (p <0.01), sum of 10 skinfolds (p <0.01), abdominal visceral fat (p <0.01), fasting plasma triglycerides (p <0.05) and cholesterol (p <0.05), maximal oxygen uptake (p <0.05), and respiratory exchange ratio during submaximal work (p <0.01). We conclude that even though there were large individual differences in response to the negative energy balance and exercise protocol, subjects with the same genotype were more alike in responses than subjects with different genotypes particularly for body fat, body energy, and abdominal visceral fat changes. High lipid oxidizers and low lipid oxidizers during sub-maximal exercise were also seen despite the fact that all subjects had experienced the same exercise and nutritional conditions for about three months. 相似文献
28.
29.
Lorenz Schmid Michel Bottlaender Chantal Fuseau Denis Fournier Emmanuel Brouillet Mariannick Mazire 《Journal of neurochemistry》1995,65(4):1880-1886
Abstract: The distinctive pharmacological activity of zolpidem in rats compared with classical benzodiazepines has been related to its differential affinity for benzodiazepine receptor (BZR) subtypes. By contrast, in nonhuman primates the pharmacological activity of zolpidem was found to be quite similar to that of classical BZR agonists. In an attempt to explain this discrepancy, we examined the ability of zolpidem to differentiate BZR subtypes in vivo in primate brain using positron emission tomography. The BZRs were specifically labeled with [11C]flumazenil. Radiotracer displacement by zolpidem was monophasic in cerebellum and neocortex, with in vivo Hill coefficients close to 1. Conversely, displacement of [11C]flumazenil was biphasic in hippocampus, amygdala, septum, insula, striatum, and pons, with Hill coefficients significantly smaller than 1, suggesting two different binding sites for zolpidem. In these cerebral regions, the half-maximal inhibitory doses for the high-affinity binding site were similar to those found in cerebellum and neocortex and ~100-fold higher for the low-affinity binding site. The low-affinity binding site accounted for <32% of the specific [11C]-flumazenil binding. Such zolpidem binding characteristics contrast with those reported for rodents, where three different binding sites were found. Species differences in binding characteristics may explain why zolpidem has a distinctive pharmacological activity in rodents, whereas its pharmacological activity in primates is quite similar to that of classical BZR agonists, except for the absence of severe effects on memory functions, which may be due to the lack of substantial zolpidem affinity for a distinct BZR subtype in cerebral structures belonging to the limbic system. 相似文献
30.
Magali Basille Bruno J. Gonzalez Laurence Desrues †Myriam Demas ‡Alain Fournier Hubert Vaudry 《Journal of neurochemistry》1995,65(3):1318-1324
Abstract: The presence of receptors for the novel neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP) has been recently demonstrated in the external granule cell layer of the cerebellum, a germinative matrix that generates the majority of cerebellar interneurons. In the present study, we have taken advantage of the possibility of obtaining a culture preparation that is greatly enriched in immature cerebellar granule cells to investigate the effect of PACAP on the adenylyl cyclase and phospholipase C transduction pathways. The two molecular forms of PACAP, i.e., 27-(PACAP27) and 38-(PACAP38) amino-acid forms of PACAP, induced a dose-dependent stimulation of cyclic AMP production in granule cells. The potencies of PACAP27 and PACAP38 were similar (ED50 = 0.12 ± 0.01 and 0.23 ± 0.07 n M , respectively), whereas vasoactive intestinal polypeptide (VIP) was ∼100 times less potent. PACAP27 and PACAP38 also induced a dose-dependent stimulation of polyphosphoinositide breakdown (ED50 = 19.1 ± 6.3 and 13.4 ± 6.0 n M , respectively), whereas VIP had no effect on polyphosphoinositide metabolism. The effect of PACAP38 on inositol phosphate formation was significantly reduced by U-73122 and by pertussis toxin, indicating that activation of PACAP receptors causes stimulation of a phospholipase C through a pertussis toxin-sensitive G protein. In contrast, forskolin and dibutyryl cyclic AMP did not affect PACAP-induced stimulation of inositol phosphates. Taken together, the present results demonstrate that PACAP stimulates independently the adenylyl cyclase and the phospholipase C transduction pathways in immature cerebellar granule cells. These data favor the concept that PACAP may play important roles in the control of proliferation and/or differentiation of cerebellar neuroblasts. 相似文献