全文获取类型
收费全文 | 67110篇 |
免费 | 7110篇 |
国内免费 | 22篇 |
出版年
2022年 | 600篇 |
2021年 | 1327篇 |
2020年 | 788篇 |
2019年 | 993篇 |
2018年 | 1190篇 |
2017年 | 1018篇 |
2016年 | 1648篇 |
2015年 | 2698篇 |
2014年 | 3000篇 |
2013年 | 3366篇 |
2012年 | 4543篇 |
2011年 | 4166篇 |
2010年 | 2674篇 |
2009年 | 2367篇 |
2008年 | 3449篇 |
2007年 | 3389篇 |
2006年 | 3088篇 |
2005年 | 2936篇 |
2004年 | 2757篇 |
2003年 | 2655篇 |
2002年 | 2502篇 |
2001年 | 1251篇 |
2000年 | 1146篇 |
1999年 | 1112篇 |
1998年 | 820篇 |
1997年 | 649篇 |
1996年 | 610篇 |
1995年 | 523篇 |
1994年 | 533篇 |
1993年 | 553篇 |
1992年 | 898篇 |
1991年 | 829篇 |
1990年 | 799篇 |
1989年 | 822篇 |
1988年 | 735篇 |
1987年 | 762篇 |
1986年 | 601篇 |
1985年 | 689篇 |
1984年 | 641篇 |
1983年 | 505篇 |
1982年 | 547篇 |
1981年 | 502篇 |
1980年 | 456篇 |
1979年 | 538篇 |
1978年 | 488篇 |
1977年 | 434篇 |
1976年 | 393篇 |
1975年 | 402篇 |
1974年 | 453篇 |
1973年 | 444篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
1.
Annie Arguello XiaoYong Yang Daniel Vogt Amelia Stanco John L. R. Rubenstein Benjamin N. R. Cheyette 《PloS one》2013,8(6)
Synaptogenesis has been extensively studied along with dendritic spine development in glutamatergic pyramidal neurons, however synapse development in cortical interneurons, which are largely aspiny, is comparatively less well understood. Dact1, one of 3 paralogous Dact (Dapper/Frodo) family members in mammals, is a scaffold protein implicated in both the Wnt/β-catenin and the Wnt/Planar Cell Polarity pathways. We show here that Dact1 is expressed in immature cortical interneurons. Although Dact1 is first expressed in interneuron precursors during proliferative and migratory stages, constitutive Dact1 mutant mice have no major defects in numbers or migration of these neurons. However, cultured cortical interneurons derived from these mice have reduced numbers of excitatory synapses on their dendrites. We selectively eliminated Dact1 from mouse cortical interneurons using a conditional knock-out strategy with a Dlx-I12b enhancer-Cre allele, and thereby demonstrate a cell-autonomous role for Dact1 during postsynaptic development. Confirming this cell-autonomous role, we show that synapse numbers in Dact1 deficient cortical interneurons are rescued by virally-mediated re-expression of Dact1 specifically targeted to these cells. Synapse numbers in these neurons are also rescued by similarly targeted expression of the Dact1 binding partner Dishevelled-1, and partially rescued by expression of Disrupted in Schizophrenia-1, a synaptic protein genetically implicated in susceptibility to several major mental illnesses. In sum, our results support a novel cell-autonomous postsynaptic role for Dact1, in cooperation with Dishevelled-1 and possibly Disrupted in Schizophrenia-1, in the formation of synapses on cortical interneuron dendrites. 相似文献
2.
T Smith 《BMJ (Clinical research ed.)》1984,289(6449):909-910
3.
4.
Andrew C Smith 《BMJ (Clinical research ed.)》1981,283(6306):1596-1597
5.
Escherichia coli RecBC pseudorevertants lacking chi recombinational hotspot activity 总被引:24,自引:7,他引:17 下载免费PDF全文
Pseudorevertants of an Escherichia coli exonuclease V (RecBC enzyme)-negative mutant have been isolated after ethyl methane sulfonate mutagenesis of a recC73 (presumed missense) mutant. The remedial mutations in each of the four pseudorevertants studied in detail map and complement as recC mutations. By several criteria, such as recombination proficiency, support of phage growth, RecBC nuclease activity, and cell viability, the pseudorevertants appear to have regained partially or completely various aspects of RecBC activity. However, chi recombinational hotspots, which stimulate exclusively the RecBC pathway of recombination, have no detectable activity in lambda vegetative crosses in the pseudorevertants. The properties of these mutants, in which the RecBC pathway of recombination is active yet in which chi is not active, are consistent with the hypothesis that wild-type RecBC enzyme directly interacts with chi sites; alternatively, the mutants may block or bypass the productive interaction of another recombinational enzyme with chi. 相似文献
6.
T Smith 《BMJ (Clinical research ed.)》1980,281(6252):1410-1411
7.
Myoglobin (Mb) is the classic vertebrate oxygen-binding protein present in aerobic striated muscles. It functions principally in oxygen delivery and provides muscle with its characteristic red colour. Members of the Antarctic icefish family (Channichthyidae) are widely thought to be extraordinary for lacking cardiac Mb expression, a fact that has been attributed to their low metabolic rate and unusual evolutionary history. Here, we report that cardiac Mb deficit, associated with pale heart colour, has evolved repeatedly during teleost evolution. This trait affects both gill- and air-breathing species from temperate to tropical habitats across a full range of salinities. Cardiac Mb deficit results from total pseudogenization in three-spined stickleback and is associated with a massive reduction in mRNA level in two species that evidently retain functional Mb. The results suggest that near or complete absence of Mb-assisted oxygen delivery to heart muscle is a common facet of teleost biodiversity, even affecting lineages with notable oxygen demands. We suggest that Mb deficit may affect how different teleost species deal with increased tissue oxygen demands arising under climate change. 相似文献
8.
Selective diapedesis of Th1 cells induced by endothelial cell RANTES. 总被引:16,自引:0,他引:16
T Kawai M Seki K Hiromatsu J W Eastcott G F Watts M Sugai D J Smith S A Porcelli M A Taubman 《Journal of immunology (Baltimore, Md. : 1950)》1999,163(6):3269-3278
Differentiated CD4 T cells can be divided into Th1 and Th2 types based on the cytokines they produce. Differential expression of chemokine receptors on either the Th1-type or the Th2-type cell suggests that Th1-type and Th2-type cells differ not only in cytokine production but also in their migratory capacity. Stimulation of endothelial cells with IFN-gamma selectively enhanced transmigration of Th1-type cells, but not Th2-type cells, in a transendothelial migration assay. Enhanced transmigration of Th1-type cells was dependent on the chemokine RANTES produced by endothelial cells, as indicated by the findings that Ab neutralizing RANTES, or Ab to its receptor CCR5, inhibited transmigration. Neutralizing Ab to chemokines macrophage-inflammatory protein-1alpha or monocyte chemotactic protein-1 did not inhibit Th1 selective migration. Whereas anti-CD18 and anti-CD54 blocked basal levels of Th1-type cell adherence to endothelial cells and also inhibited transmigration, anti-RANTES blocked only transmigration, indicating that RANTES appeared to induce transmigration of adherent T cells. RANTES seemed to promote diapedesis of adherent Th1-type cells by augmenting pseudopod formation in conjunction with actin rearrangement by a pathway that was sensitive to the phosphoinositol 3-kinase inhibitor wortmannin and to the Rho GTP-binding protein inhibitor, epidermal cell differentiation inhibitor. Thus, enhancement of Th1-type selective migration appeared to be responsible for the diapedesis induced by interaction between CCR5 on Th1-type cells and RANTES produced by endothelial cells. Further evidence that CCR5 and RANTES play a modulatory role in Th1-type selective migration derives from the abrogation of this migration by anti-RANTES and anti-CCR5 Abs. 相似文献
9.
10.
S. Wehmeier A. S. Varghese S. S. Gurcha B. Tissot M. Panico P. Hitchen H. R. Morris G. S. Besra A. Dell M. C. M. Smith 《Molecular microbiology》2009,71(2):421-433
Previously mutations in a putative protein O -mannosyltransferase (SCO3154, Pmt) and a polyprenol phosphate mannose synthase (SCO1423, Ppm1) were found to cause resistance to phage, φC31, in the antibiotic producing bacteria Streptomyces coelicolor A3(2). It was proposed that these two enzymes were part of a protein O-glycosylation pathway that was necessary for synthesis of the phage receptor. Here we provide the evidence that Pmt and Ppm1 are indeed both required for protein O-glycosylation. The phosphate binding protein PstS was found to be glycosylated with a trihexose in the S. coelicolor parent strain, J1929, but not in the pmt − derivative, DT1025. Ppm1 was necessary for the transfer of mannose to endogenous polyprenol phosphate in membrane preparations of S. coelicolor . A mutation in ppm1 that conferred an E218V substitution in Ppm1 abolished mannose transfer and glycosylation of PstS. Mass spectrometry analysis of extracted lipids showed the presence of a glycosylated polyprenol phosphate (PP) containing nine repeated isoprenyl units (C45 -PP). S. coelicolor membranes were also able to catalyse the transfer of mannose to peptides derived from PstS, indicating that these could be targets for Pmt in vivo . 相似文献