全文获取类型
收费全文 | 1000篇 |
免费 | 116篇 |
国内免费 | 3篇 |
出版年
2022年 | 7篇 |
2021年 | 11篇 |
2020年 | 8篇 |
2019年 | 8篇 |
2018年 | 7篇 |
2017年 | 11篇 |
2016年 | 15篇 |
2015年 | 27篇 |
2014年 | 27篇 |
2013年 | 44篇 |
2012年 | 52篇 |
2011年 | 43篇 |
2010年 | 34篇 |
2009年 | 36篇 |
2008年 | 34篇 |
2007年 | 48篇 |
2006年 | 39篇 |
2005年 | 37篇 |
2004年 | 38篇 |
2003年 | 38篇 |
2002年 | 34篇 |
2001年 | 29篇 |
2000年 | 31篇 |
1999年 | 34篇 |
1998年 | 13篇 |
1997年 | 21篇 |
1996年 | 12篇 |
1994年 | 9篇 |
1993年 | 15篇 |
1992年 | 23篇 |
1991年 | 22篇 |
1990年 | 15篇 |
1989年 | 26篇 |
1988年 | 20篇 |
1987年 | 14篇 |
1986年 | 21篇 |
1985年 | 15篇 |
1984年 | 9篇 |
1983年 | 13篇 |
1982年 | 13篇 |
1981年 | 16篇 |
1980年 | 9篇 |
1979年 | 11篇 |
1978年 | 9篇 |
1976年 | 8篇 |
1975年 | 7篇 |
1974年 | 10篇 |
1973年 | 10篇 |
1970年 | 8篇 |
1968年 | 7篇 |
排序方式: 共有1119条查询结果,搜索用时 437 毫秒
141.
142.
Williams WP Gibson EM Wang C Tjho S Khattar N Bentley GE Tsutsui K Kriegsfeld LJ 《Integrative and comparative biology》2009,49(5):519-537
Circadian rhythms impact a variety of behavioral and physiological functions contributing to longevity and successful reproduction. In their natural environments, individuals of a species are faced with a multitude of challenges and the coordination of internal processes and behavior with external pressures has been hypothesized to be an important target of natural selection. Several lines of evidence from cyanobacteria, Drosophila, and plants provide strong support for an important role of the circadian clock in survival and reproductive success. Similarly in mammals, disruptions in circadian function markedly impact reproduction and lifespan. The present review discusses research outlining the proximate and ultimate mechanisms responsible for the central and peripheral control of the reproductive axis. Because precise temporal coordination of the endocrine system is particularly crucial for reproduction by females, the present overview focuses on the role of circadian timing in this sex. 相似文献
143.
The sequences of both of the human sex chromosomes and of a substantial part of the chimpanzee Y chromosome have now been determined, and most of the protein-coding genes have been identified. The X chromosome codes for more than 800 proteins but the Y chromosome for only approximately 60, illustrating their very different evolutionary histories since their origin from an autosomal pair approximately 300 million years ago and explaining their differential importance in disease. These sequences have provided the basis for understanding normal patterns of variation, such as the distribution of SNPs, and patterns of linkage disequilibrium. In addition, they have been useful for identifying variants associated with simple Mendelian disorders such as microphthalmia or mental retardation, and more complex disorders such as osteoporosis. 相似文献
144.
Bentley DR 《Current opinion in genetics & development》2006,16(6):545-552
DNA sequencing can be used to gain important information on genes, genetic variation and gene function for biological and medical studies. The growing collection of publicly available reference genome sequences will underpin a new era of whole genome re-sequencing, but sequencing costs need to fall and throughput needs to rise by several orders of magnitude. Novel technologies are being developed to meet this need by generating massive amounts of sequence that can be aligned to the reference sequence. The challenge is to maintain the high standards of accuracy and completeness that are hallmarks of the previous genome projects. One or more new sequencing technologies are expected to become the mainstay of future research, and to make DNA sequencing centre stage as a routine tool in genetic research in the coming years. 相似文献
145.
A ratiometric fluorescent chemosensor 5 was designed and synthesized based on internal charge transfer (ICT). The indicator absorbs and emits light in the visible wavelength range. In acetonitrile, blue shifts in fluorescent emission upon zinc binding are due to the formation of a 1:2 metal/ligand complex, which induced a fluorescent emission at 616 nm at the expense of the fluorescent emission at 672 nm. 相似文献
146.
Bentley M Liang Y Mullen K Xu D Sztul E Hay JC 《The Journal of biological chemistry》2006,281(50):38825-38833
In mammals, coat complex II (COPII)-coated transport vesicles deliver secretory cargo to vesicular tubular clusters (VTCs) that facilitate cargo sorting and transport to the Golgi. We documented in vitro tethering and SNARE-dependent homotypic fusion of endoplasmic reticulum-derived COPII transport vesicles to form larger cargo containers characteristic of VTCs ( Xu, D., and Hay, J. C. (2004) J. Cell Biol. 167, 997-1003). COPII vesicles thus appear to contain all necessary components for homotypic tethering and fusion, providing a pathway for de novo VTC biogenesis. Here we demonstrate that antibodies against the endoplasmic reticulum/Golgi SNARE Syntaxin 5 inhibit COPII vesicle homotypic tethering as well as fusion, implying an unanticipated role for SNAREs upstream of fusion. Inhibition of SNARE complex access and/or disassembly with dominant-negative alpha-soluble NSF attachment protein (SNAP) also inhibited tethering, implicating SNARE status as a critical determinant in COPII vesicle tethering. The tethering-defective vesicles generated in the presence of dominant-negative alpha-SNAP specifically lacked the Rab1 effectors p115 and GM130 but not other peripheral membrane proteins. Furthermore, Rab effectors, including p115, were shown to be required for homotypic COPII vesicle tethering. Thus, our results demonstrate a requirement for SNARE-dependent tether recruitment and function in COPII vesicle fusion. We anticipate that recruitment of tether molecules by an upstream SNARE signal ensures that tethering events are initiated only at focal sites containing appropriately poised fusion machinery. 相似文献
147.
Joellen M. Schildkraut Edwin S. Iversen Melanie A. Wilson Merlise A. Clyde Patricia G. Moorman Rachel T. Palmieri Regina Whitaker Rex C. Bentley Jeffrey R. Marks Andrew Berchuck 《PloS one》2010,5(4)
Background
We analyzed the association between 53 genes related to DNA repair and p53-mediated damage response and serous ovarian cancer risk using case-control data from the North Carolina Ovarian Cancer Study (NCOCS), a population-based, case-control study.Methods/Principal Findings
The analysis was restricted to 364 invasive serous ovarian cancer cases and 761 controls of white, non-Hispanic race. Statistical analysis was two staged: a screen using marginal Bayes factors (BFs) for 484 SNPs and a modeling stage in which we calculated multivariate adjusted posterior probabilities of association for 77 SNPs that passed the screen. These probabilities were conditional on subject age at diagnosis/interview, batch, a DNA quality metric and genotypes of other SNPs and allowed for uncertainty in the genetic parameterizations of the SNPs and number of associated SNPs. Six SNPs had Bayes factors greater than 10 in favor of an association with invasive serous ovarian cancer. These included rs5762746 (median OR(odds ratio)per allele = 0.66; 95% credible interval (CI) = 0.44–1.00) and rs6005835 (median ORper allele = 0.69; 95% CI = 0.53–0.91) in CHEK2, rs2078486 (median ORper allele = 1.65; 95% CI = 1.21–2.25) and rs12951053 (median ORper allele = 1.65; 95% CI = 1.20–2.26) in TP53, rs411697 (median OR rare homozygote = 0.53; 95% CI = 0.35 – 0.79) in BACH1 and rs10131 (median OR rare homozygote = not estimable) in LIG4. The six most highly associated SNPs are either predicted to be functionally significant or are in LD with such a variant. The variants in TP53 were confirmed to be associated in a large follow-up study.Conclusions/Significance
Based on our findings, further follow-up of the DNA repair and response pathways in a larger dataset is warranted to confirm these results. 相似文献148.
John P. Bentley Folkert W. Asselbergs Christopher S. Coffey Patricia R. Hebert Jason H. Moore Hans L. Hillege Wiek H. van Gilst 《PloS one》2010,5(9)
Background
Vascular fibrinolytic balance is maintained primarily by interplay of tissue plasminogen activator (t-PA) and plasminogen activator inhibitor type 1 (PAI-1). Previous research has shown that polymorphisms in genes from the renin-angiotensin (RA), bradykinin, and fibrinolytic systems affect plasma concentrations of both t-PA and PAI-1 through a set of gene-gene interactions. In the present study, we extend this finding by exploring the effects of polymorphisms in genes from these systems on incident cardiovascular disease, explicitly examining two-way interactions in a large population-based study.Methodology/Principal Findings
Data from the population-based PREVEND study in Groningen, The Netherlands (n = 8,138) were analyzed. The effects of the polymorphisms and their interactions on cardiovascular events were analyzed via Cox proportional hazards models. There was no association between five of the six polymorphisms singly and risk of cardiovascular disease. There was a significant main effect for the ACE I/D polymorphism for both dominant and additive coding schemes. There were significant interactions between the following polymorphism pairs even after adjustment for known risk factors: ACE I/D & PAI-1 4G/5G (p = 0.012), BDKRB2 C181T & ACE I/D (p = 0.016), BDKRB2 C58T & ACE I/D (p = 0.025), BDKRB2 exon 1 I/D & AT1R A1166C (p = 0.017), and BDKRB2 C58T & AT1R A1166C (p = 0.015).Conclusions/Significance
This study suggests possible interactions between genes from the RA, bradykinin, and fibrinolytic systems on the risk of cardiovascular disease, extending previous research that has demonstrated that interactions among genes from these systems influence plasma concentrations of both t-PA and PAI-1. Further explorations of these interactions are needed. 相似文献149.
Woodruff JA Lacey EA Bentley G 《Journal of experimental zoology. Part A, Ecological genetics and physiology》2010,313(8):498-507
The environment in which an animal lives can profoundly influence its biology, including physiological responses to external stressors. To examine the effects of environmental conditions on physiological stress reactions in colonial tuco-tucos (Ctenomys sociabilis), we measured glucocorticoid (GC) levels in captive and free-living members of this species of social, subterranean rodent. Analyses of plasma and fecal samples revealed immunoreactive corticosterone (metabolites) to be the most prevalent GC in this species. An adrenocorticotropic hormone challenge confirmed that fecal corticosterone metabolites are responsive to exogenous stressors and provided validation of the commercial enzyme immunoassay kit used to detect these metabolites. Comparisons of adult female C. sociabilis from natural and captive environments revealed significantly higher baseline concentrations of corticosterone metabolites and significantly greater individual variation in metabolite concentrations among free-living animals. These findings suggest that the natural environment in which these animals occur is more challenging and more variable than the captive housing conditions employed. In addition to providing the first evaluation of GC levels in captive and wild colonial tuco-tucos, our findings indicate that the influence of environmental conditions on stress physiology may have important implications for understanding the social behavior of this species in the laboratory and the field. 相似文献
150.
Daniel J. Barnett Roger Levine Carol B. Thompson Gamunu U. Wijetunge Anthony L. Oliver Melissa A. Bentley Patrick D. Neubert Ronald G. Pirrallo Jonathan M. Links Ran D. Balicer 《PloS one》2010,5(3)