全文获取类型
收费全文 | 15540篇 |
免费 | 1535篇 |
国内免费 | 2篇 |
出版年
2024年 | 12篇 |
2023年 | 85篇 |
2022年 | 193篇 |
2021年 | 375篇 |
2020年 | 233篇 |
2019年 | 273篇 |
2018年 | 324篇 |
2017年 | 294篇 |
2016年 | 507篇 |
2015年 | 955篇 |
2014年 | 924篇 |
2013年 | 1128篇 |
2012年 | 1468篇 |
2011年 | 1403篇 |
2010年 | 894篇 |
2009年 | 767篇 |
2008年 | 995篇 |
2007年 | 993篇 |
2006年 | 946篇 |
2005年 | 903篇 |
2004年 | 859篇 |
2003年 | 740篇 |
2002年 | 679篇 |
2001年 | 112篇 |
2000年 | 69篇 |
1999年 | 113篇 |
1998年 | 135篇 |
1997年 | 76篇 |
1996年 | 73篇 |
1995年 | 53篇 |
1994年 | 54篇 |
1993年 | 52篇 |
1992年 | 36篇 |
1991年 | 45篇 |
1990年 | 30篇 |
1989年 | 16篇 |
1988年 | 31篇 |
1987年 | 15篇 |
1986年 | 16篇 |
1985年 | 18篇 |
1984年 | 14篇 |
1983年 | 17篇 |
1982年 | 20篇 |
1981年 | 12篇 |
1980年 | 16篇 |
1979年 | 7篇 |
1978年 | 12篇 |
1977年 | 14篇 |
1976年 | 7篇 |
1974年 | 11篇 |
排序方式: 共有10000条查询结果,搜索用时 453 毫秒
881.
882.
883.
884.
885.
While K-ras is essential for mouse development, expression of the K-ras 4A splice variant is dispensable
下载免费PDF全文
![点击此处可从《Molecular and cellular biology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Plowman SJ Williamson DJ O'Sullivan MJ Doig J Ritchie AM Harrison DJ Melton DW Arends MJ Hooper ML Patek CE 《Molecular and cellular biology》2003,23(24):9245-9250
In mammals, the three classical ras genes encode four highly homologous proteins, N-Ras, H-Ras, and the isoforms K-Ras 4A and 4B. Previous studies have shown that K-ras is essential for mouse development and that while K-ras 4A and 4B are expressed during development, K-ras 4A expression is regulated temporally and spatially and occurs in adult kidney, intestine, stomach, and liver. In the present study, the pattern of K-ras 4A expression was examined in a wide range of wild-type adult mouse tissues, and gene targeting was used to generate K-ras 4A-deficient mice to examine its role in development. It was found that K-ras 4A is also expressed in uterus, lung, pancreas, salivary glands, seminal vesicles, bone marrow cells, and cecum, where it was the major K-Ras isoform expressed. Mating between K-ras(tmDelta4A/+) mice produced viable K-ras(tmDelta4A/tmDelta4A) offspring with the expected Mendelian ratios of inheritance, and these mice expressed the K-ras 4B splice variant only. K-ras(tmDelta4A/tmDelta4A) mice were fertile and showed no histopathological abnormalities on inbred (129/Ola) or crossbred (129/Ola x C57BL/6) genetic backgrounds. The results demonstrate that K-Ras 4A, like H- and N-Ras, is dispensable for normal mouse development, at least in the presence of functional K-Ras 4B. 相似文献
886.
Li J Hawkins IC Harvey CD Jennings JL Link AJ Patton JG 《Molecular and cellular biology》2003,23(21):7437-7447
SRrp86 is a unique member of the SR protein superfamily containing one RNA recognition motif and two serine-arginine (SR)-rich domains separated by an unusual glutamic acid-lysine (EK)-rich region. Previously, we showed that SRrp86 could regulate alternative splicing by both positively and negatively modulating the activity of other SR proteins and that the unique EK domain could inhibit both constitutive and alternative splicing. These functions were most consistent with the model in which SRrp86 functions by interacting with and thereby modulating the activity of target proteins. To identify the specific proteins that interact with SRrp86, we used a yeast two-hybrid library screen and immunoprecipitation coupled to mass spectrometry. We show that SRrp86 interacts with all of the core SR proteins, as well as a subset of other splicing regulatory proteins, including SAF-B, hnRNP G, YB-1, and p72. In contrast to previous results that showed activation of SRp20 by SRrp86, we now show that SAF-B, hnRNP G, and 9G8 all antagonize the activity of SRrp86. Overall, we conclude that not only does SRrp86 regulate SR protein activity but that it is, in turn, regulated by other splicing factors to control alternative splice site selection. 相似文献
887.
Zlotorynski E Rahat A Skaug J Ben-Porat N Ozeri E Hershberg R Levi A Scherer SW Margalit H Kerem B 《Molecular and cellular biology》2003,23(20):7143-7151
Fragile sites are specific loci that form gaps, constrictions, and breaks on chromosomes exposed to partial replication stress and are rearranged in tumors. Fragile sites are classified as rare or common, depending on their induction and frequency within the population. The molecular basis of rare fragile sites is associated with expanded repeats capable of adopting unusual non-B DNA structures that can perturb DNA replication. The molecular basis of common fragile sites was unknown. Fragile sites from R-bands are enriched in flexible sequences relative to nonfragile regions from the same chromosomal bands. Here we cloned FRA7E, a common fragile site mapped to a G-band, and revealed a significant difference between its flexibility and that of nonfragile regions mapped to G-bands, similar to the pattern found in R-bands. Thus, in the entire genome, flexible sequences might play a role in the mechanism of fragility. The flexible sequences are composed of interrupted runs of AT-dinucleotides, which have the potential to form secondary structures and hence can affect replication. These sequences show similarity to the AT-rich minisatellite repeats that underlie the fragility of the rare fragile sites FRA16B and FRA10B. We further demonstrate that the normal alleles of FRA16B and FRA10B span the same genomic regions as the common fragile sites FRA16C and FRA10E. Our results suggest that a shared molecular basis, conferred by sequences with a potential to form secondary structures that can perturb replication, may underlie the fragility of rare fragile sites harboring AT-rich minisatellite repeats and aphidicolin-induced common fragile sites. 相似文献
888.
A unique autophosphorylation site on Tie2/Tek mediates Dok-R phosphotyrosine binding domain binding and function
下载免费PDF全文
![点击此处可从《Molecular and cellular biology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Jones N Chen SH Sturk C Master Z Tran J Kerbel RS Dumont DJ 《Molecular and cellular biology》2003,23(8):2658-2668
Tie2/Tek is an endothelial cell receptor tyrosine kinase that induces signal transduction pathways involved in cell migration upon angiopoietin-1 (Ang1) stimulation. To address the importance of the various tyrosine residues of Tie2 in signal transduction, we generated a series of Tie2 mutants and examined their signaling properties. Using this approach in conjunction with a phosphorylation state-specific antibody, we identified tyrosine residue 1106 on Tie2 as an Ang1-dependent autophosphorylation site that mediates binding and phosphorylation of the downstream-of-kinase-related (Dok-R) docking protein. This tyrosine residue is contained within a unique interaction motif for the phosphotyrosine binding domain of Dok-R, and the pleckstrin homology domain of Dok-R further contributes to Tie2 binding in a phosphatidylinositol 3'-kinase-dependent manner. Introduction of a Tie2 mutant lacking tyrosine residue 1106 into endothelial cells interferes with Dok-R phosphorylation in response to Ang1. Furthermore, this mutant is unable to restore the migration potential of endothelial cells derived from mice lacking Tie2. Together, these findings demonstrate that tyrosine residue 1106 on Tie2 is critical for coupling downstream cell migration signal transduction pathways with Ang1 stimulation in endothelial cells. 相似文献
889.
Protein-protein dimerization is ubiquitous in biology, but its role in self-organization remains unexplored. Here we use Monte Carlo simulations to demonstrate that under diffusion-limited conditions, reversible dimerization alone can cause membrane proteins to cluster into oligomer-like structures. When multiple distinct protein species are able to form dimers, then heterodimerization and homodimerization can organize proteins into structured clusters that can affect cellular physiology. As an example, we demonstrate how receptor dimerization could provide a physical mechanism for regulating information flow by controlling receptor-receptor cross talk. These results are physically realistic for some membrane proteins, including members of the G-protein coupled receptor family, and may provide a physiological reason as to why many proteins dimerize. 相似文献
890.
Martha R. Weiss Eric M. Lind Meg T. Jones Jeremy D. Long Jennifer L. Maupin 《Journal of Insect Behavior》2003,16(4):465-480
Larvae of the silver-spotted skipper, Epargyreus clarus (Hesperiidae), construct shelters from leaves of their leguminous host plants, making four distinct shelter types that change predictably over larval ontogeny. Shelters built by first-instar larvae are located on the apical half of the leaflet and are almost invariant in size, shape, and orientation, suggesting a stereotypical process of shelter location and construction. We have determined that the regularity of these shelters results from a prescribed pattern of larval movements and behaviors, in which larvae use their body length as a ruler and employ silk not only as a building material but also as a template to guide the location of cuts in the leaf. Though lepidopteran larvae lack the sensitive antennae, long jointed appendages, and other measurement devices used by structure-building bees, wasps, and caddis flies, they can nonetheless use simple tools and behavioral patterns to produce characteristic and regular shelters. 相似文献