全文获取类型
收费全文 | 3042篇 |
免费 | 272篇 |
国内免费 | 2篇 |
出版年
2024年 | 5篇 |
2023年 | 28篇 |
2022年 | 69篇 |
2021年 | 132篇 |
2020年 | 77篇 |
2019年 | 105篇 |
2018年 | 104篇 |
2017年 | 83篇 |
2016年 | 149篇 |
2015年 | 225篇 |
2014年 | 192篇 |
2013年 | 279篇 |
2012年 | 302篇 |
2011年 | 284篇 |
2010年 | 174篇 |
2009年 | 136篇 |
2008年 | 187篇 |
2007年 | 146篇 |
2006年 | 144篇 |
2005年 | 119篇 |
2004年 | 90篇 |
2003年 | 86篇 |
2002年 | 74篇 |
2001年 | 21篇 |
2000年 | 10篇 |
1999年 | 13篇 |
1998年 | 16篇 |
1997年 | 10篇 |
1996年 | 1篇 |
1995年 | 8篇 |
1994年 | 4篇 |
1993年 | 3篇 |
1991年 | 1篇 |
1990年 | 1篇 |
1989年 | 3篇 |
1988年 | 5篇 |
1987年 | 1篇 |
1986年 | 2篇 |
1985年 | 8篇 |
1984年 | 4篇 |
1982年 | 1篇 |
1981年 | 1篇 |
1980年 | 1篇 |
1978年 | 4篇 |
1975年 | 1篇 |
1974年 | 1篇 |
1973年 | 3篇 |
1971年 | 1篇 |
1967年 | 1篇 |
1961年 | 1篇 |
排序方式: 共有3316条查询结果,搜索用时 15 毫秒
61.
62.
63.
Matthew L. Rook Megan Miaro Tyler Couch Dana L. Kneisley Maria Musgaard David M. MacLean 《The Journal of general physiology》2021,153(8)
Desensitization is a common feature of ligand-gated ion channels, although the molecular cause varies widely between channel types. Mutations that greatly reduce or nearly abolish desensitization have been described for many ligand-gated ion channels, including glutamate, GABA, glycine, and nicotinic receptors, but not for acid-sensing ion channels (ASICs) until recently. Mutating Gln276 to a glycine (Q276G) in human ASIC1a was reported to mostly abolish desensitization at both the macroscopic and the single channel levels, potentially providing a valuable tool for subsequent studies. However, we find that in both human and chicken ASIC1, the effect of Q276G is modest. In chicken ASIC1, the equivalent Q277G slightly reduces desensitization when using pH 6.5 as a stimulus but desensitizes, essentially like wild-type, when using more acidic pH values. In addition, steady-state desensitization is intact, albeit right-shifted, and recovery from desensitization is accelerated. Molecular dynamics simulations indicate that the Gln277 side chain participates in a hydrogen bond network that might stabilize the desensitized conformation. Consistent with this, destabilizing this network with the Q277N or Q277L mutations largely mimics the Q277G phenotype. In human ASIC1a, the Q276G mutation also reduces desensitization, but not to the extent reported previously. Interestingly, the kinetic consequences of Q276G depend on the human variant used. In the common G212 variant, Q276G slows desensitization, while in the rare D212 variant desensitization accelerates. Our data reveal that while the Q/G mutation does not abolish or substantially impair desensitization as previously reported, it does point to unexpected differences between chicken and human ASICs and the need for careful scrutiny before using this mutation in future studies. 相似文献
64.
The myometrium is the smooth muscle layer of the uterus that generates the contractions that drive processes such as menstruation and childbirth. Aberrant contractions of the myometrium can result in preterm birth, insufficient progression of labor, or other difficulties that can lead to maternal or fetal complications or even death. To investigate the underlying mechanisms of these conditions, the most common model systems have conventionally been animal models and human tissue strips, which have limitations mostly related to relevance and scalability, respectively. Myometrial smooth muscle cells have also been isolated from patient biopsies and cultured in vitro as a more controlled experimental system. However, in vitro approaches have focused primarily on measuring the effects of biochemical stimuli and neglected biomechanical stimuli, despite the extensive evidence indicating that remodeling of tissue rigidity or excessive strain is associated with uterine disorders. In this review, we first describe the existing approaches for modeling human myometrium with animal models and human tissue strips and compare their advantages and disadvantages. Next, we introduce existing in vitro techniques and assays for assessing contractility and summarize their applications in elucidating the role of biochemical or biomechanical stimuli on human myometrium. Finally, we conclude by proposing the translation of “organ on chip” approaches to myometrial smooth muscle cells as new paradigms for establishing their fundamental mechanobiology and to serve as next-generation platforms for drug development. 相似文献
65.
66.
Lisa R. Goldberg Emily J. Yao Julia C. Kelliher Eric R. Reed Jiayi Wu Cox Cory Parks Stacey L. Kirkpatrick Jacob A. Beierle Melanie M. Chen William E. Johnson Gregg E. Homanics Robert W. Williams Camron D. Bryant Megan K. Mulligan 《Genes, Brain & Behavior》2021,20(8):e12774
Psychostimulant (methamphetamine, cocaine) use disorders have a genetic component that remains mostly unknown. We conducted genome-wide quantitative trait locus (QTL) analysis of methamphetamine stimulant sensitivity. To facilitate gene identification, we employed a Reduced Complexity Cross between closely related C57BL/6 mouse substrains and examined maximum speed and distance traveled over 30 min following methamphetamine (2 mg/kg, i.p.). For maximum methamphetamine-induced speed following the second and third administration, we identified a single genome-wide significant QTL on chromosome 11 that peaked near the Cyfip2 locus (LOD = 3.5, 4.2; peak = 21 cM [36 Mb]). For methamphetamine-induced distance traveled following the first and second administration, we identified a genome-wide significant QTL on chromosome 5 that peaked near a functional intronic indel in Gabra2 coding for the alpha-2 subunit of the GABA-A receptor (LOD = 3.6–5.2; peak = 34–35 cM [66–67 Mb]). Striatal cis-expression QTL mapping corroborated Gabra2 as a functional candidate gene underlying methamphetamine-induced distance traveled. CRISPR/Cas9-mediated correction of the mutant intronic deletion on the C57BL/6J background to the wild-type C57BL/6NJ allele was sufficient to reduce methamphetamine-induced locomotor activity toward the wild-type C57BL/6NJ-like level, thus validating the quantitative trait variant (QTV). These studies show the power and efficiency of Reduced Complexity Crosses in identifying causal variants underlying complex traits. Functionally restoring Gabra2 expression decreased methamphetamine stimulant sensitivity and supports preclinical and human genetic studies implicating the GABA-A receptor in psychostimulant addiction-relevant traits. Importantly, our findings have major implications for studying psychostimulants in the C57BL/6J strain—the gold standard strain in biomedical research. 相似文献
67.
Dybzinski Ray Taylor Natalie Prosser Megan Niosi Olivia Demo Madeline Kilbane Erin 《Plant Ecology》2021,222(8):977-991
Plant Ecology - Understanding resource uptake as a function of fine-root mass is important for both basic ecological theory and applied biogeochemical cycling models. We measured plant population... 相似文献
68.
Milan Vrtílek Pierre J. C. Chuard Maider Iglesias-Carrasco Zhuzhi Zhang Michael D. Jennions Megan L. Head 《Heredity》2021,127(1):52
Maternal effects are an important evolutionary force that may either facilitate adaptation to a new environment or buffer against unfavourable conditions. The degree of variation in traits expressed by siblings from different mothers is often sensitive to environmental conditions. This could generate a Maternal-by-Environment interaction (M × E) that inflates estimates of Genotype-by-Environment effects (G × E). We aimed to test for environment-specific maternal effects (M × E) using a paternal full-sib/half-sib breeding design in the seed beetle Callosobruchus maculatus, where we split and reared offspring from the same mother on two different bean host types—original and novel. Our quantitative genetic analysis indicated that maternal effects were very small on both host types for all the measured life-history traits. There was also little evidence that maternal oviposition preference for a particular host type predicted her offspring’s performance on that host. Further, additive genetic variance for most traits was relatively high on both hosts. While there was higher heritability for offspring reared in the novel host, there was no evidence for G × Es, and most cross-host genetic correlations were positive. This suggests that offspring from the same family ranked similarly for performance on both host types. Our results point to a genetic basis of host adaptation in the seed beetle, rather than maternal effects. Even so, we encourage researchers to test for potential M × Es because, due to a lack of testing, it remains unclear how often they arise.Subject terms: Evolutionary genetics, Quantitative trait 相似文献
69.
Megan J. Dobro Rachel Y. Samson Zhiheng Yu John McCullough H. Jane Ding Parkson Lee-Gau Chong Stephen D. Bell Grant J. Jensen 《Molecular biology of the cell》2013,24(15):2319-2327
The endosomal-sorting complex required for transport (ESCRT) is evolutionarily conserved from Archaea to eukaryotes. The complex drives membrane scission events in a range of processes, including cytokinesis in Metazoa and some Archaea. CdvA is the protein in Archaea that recruits ESCRT-III to the membrane. Using electron cryotomography (ECT), we find that CdvA polymerizes into helical filaments wrapped around liposomes. ESCRT-III proteins are responsible for the cinching of membranes and have been shown to assemble into helical tubes in vitro, but here we show that they also can form nested tubes and nested cones, which reveal surprisingly numerous and versatile contacts. To observe the ESCRT–CdvA complex in a physiological context, we used ECT to image the archaeon Sulfolobus acidocaldarius and observed a distinct protein belt at the leading edge of constriction furrows in dividing cells. The known dimensions of ESCRT-III proteins constrain their possible orientations within each of these structures and point to the involvement of spiraling filaments in membrane scission. 相似文献
70.
Coccinellid immigration to infested host patches influences suppression of Aphis glycines in soybean
Generalist natural enemies may be well adapted to annual crop systems in which pests and natural enemies re-colonize fields each year. In addition, for patchily-distributed pests, a natural enemy must disperse within a crop field to arrive at infested host patches. As they typically have longer generation times than their prey, theory suggests that generalist natural enemies need high immigration rates to and within fields to effectively suppress pest populations. The soybean aphid, Aphis glycines Matsumura, is a pest of an annual crop and is predominantly controlled by coccinellids. To test if rates of coccinellid arrival at aphid-infested patches are crucial for soybean aphid control, we experimentally varied coccinellid immigration to 1 m2 soybean patches using selective barriers and measured effects on A. glycines populations. In a year with low ambient aphid pressure, naturally-occurring levels of coccinellid immigration to host patches were sufficient to suppress aphid populations, while decreasing coccinellid immigration rates resulted in large increases in soybean aphid populations within infested patches. Activity of other predators was low in this year, suggesting that most of the differences in aphid population growth were due to changes in coccinellid immigration. Alternatively, in a year in which alate aphids continually colonized plots, aphid suppression was incomplete and increased activity of other predatory taxa contributed to adult coccinellid predation of A. glycines. Our results suggest that in a system in which natural enemy populations cannot track pest populations through reproduction, immigration of natural enemies to infested patches can compensate and result in pest control. 相似文献