全文获取类型
收费全文 | 669篇 |
免费 | 8篇 |
国内免费 | 4篇 |
专业分类
系统科学 | 11篇 |
教育与普及 | 1篇 |
理论与方法论 | 10篇 |
现状及发展 | 180篇 |
研究方法 | 110篇 |
综合类 | 345篇 |
自然研究 | 24篇 |
出版年
2020年 | 6篇 |
2019年 | 4篇 |
2018年 | 10篇 |
2017年 | 9篇 |
2016年 | 12篇 |
2015年 | 13篇 |
2014年 | 14篇 |
2013年 | 11篇 |
2012年 | 36篇 |
2011年 | 72篇 |
2010年 | 18篇 |
2009年 | 14篇 |
2008年 | 44篇 |
2007年 | 36篇 |
2006年 | 52篇 |
2005年 | 43篇 |
2004年 | 45篇 |
2003年 | 31篇 |
2002年 | 40篇 |
2001年 | 15篇 |
2000年 | 21篇 |
1999年 | 8篇 |
1996年 | 4篇 |
1994年 | 2篇 |
1992年 | 2篇 |
1990年 | 2篇 |
1983年 | 4篇 |
1982年 | 6篇 |
1981年 | 2篇 |
1980年 | 5篇 |
1979年 | 8篇 |
1978年 | 8篇 |
1977年 | 5篇 |
1975年 | 2篇 |
1974年 | 3篇 |
1973年 | 4篇 |
1972年 | 4篇 |
1971年 | 7篇 |
1970年 | 6篇 |
1969年 | 3篇 |
1968年 | 4篇 |
1967年 | 4篇 |
1966年 | 7篇 |
1965年 | 3篇 |
1963年 | 2篇 |
1962年 | 5篇 |
1959年 | 2篇 |
1947年 | 3篇 |
1946年 | 3篇 |
1945年 | 3篇 |
排序方式: 共有681条查询结果,搜索用时 156 毫秒
71.
Tat-specific cytotoxic T lymphocytes select for SIV escape variants during resolution of primary viraemia 总被引:55,自引:0,他引:55
Allen TM O'Connor DH Jing P Dzuris JL Mothé BR Vogel TU Dunphy E Liebl ME Emerson C Wilson N Kunstman KJ Wang X Allison DB Hughes AL Desrosiers RC Altman JD Wolinsky SM Sette A Watkins DI 《Nature》2000,407(6802):386-390
Human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) infections are characterized by early peaks of viraemia that decline as strong cellular immune responses develop. Although it has been shown that virus-specific CD8-positive cytotoxic T lymphocytes (CTLs) exert selective pressure during HIV and SIV infection, the data have been controversial. Here we show that Tat-specific CD8-positive T-lymphocyte responses select for new viral escape variants during the acute phase of infection. We sequenced the entire virus immediately after the acute phase, and found that amino-acid replacements accumulated primarily in Tat CTL epitopes. This implies that Tat-specific CTLs may be significantly involved in controlling wild-type virus replication, and suggests that responses against viral proteins that are expressed early during the viral life cycle might be attractive targets for HIV vaccine development. 相似文献
72.
Substantial efforts are focused on identifying single-nucleotide polymorphisms (SNPs) throughout the human genome, particularly in coding regions (cSNPs), for both linkage disequilibrium and association studies. Less attention, however, has been directed to the clarification of evolutionary processes that are responsible for the variability in nucleotide diversity among different regions of the genome. We report here the population sequence diversity of genomic segments within a 450-kb cluster of olfactory receptor (OR) genes on human chromosome 17. We found a dichotomy in the pattern of nucleotide diversity between OR pseudogenes and introns on the one hand and the closely interspersed intact genes on the other. We suggest that weak positive selection is responsible for the observed patterns of genetic variation. This is inferred from a lower ratio of polymorphism to divergence in genes compared with pseudogenes or introns, high non-synonymous substitution rates in OR genes, and a small but significant overall reduction in variability in the entire OR gene cluster compared with other genomic regions. The dichotomy among functionally different segments within a short genomic distance requires high recombination rates within this OR cluster. Our work demonstrates the impact of weak positive selection on human nucleotide diversity, and has implications for the evolution of the olfactory repertoire. 相似文献
73.
74.
A family of mammalian Na+-dependent L-ascorbic acid transporters. 总被引:10,自引:0,他引:10
H Tsukaguchi T Tokui B Mackenzie U V Berger X Z Chen Y Wang R F Brubaker M A Hediger 《Nature》1999,399(6731):70-75
Vitamin C (L-ascorbic acid) is essential for many enzymatic reactions, in which it serves to maintain prosthetic metal ions in their reduced forms (for example, Fe2+, Cu+), and for scavenging free radicals in order to protect tissues from oxidative damage. The facilitative sugar transporters of the GLUT type can transport the oxidized form of the vitamin, dehydroascorbic acid, but these transporters are unlikely to allow significant physiological amounts of vitamin C to be taken up in the presence of normal glucose concentrations, because the vitamin is present in plasma essentially only in its reduced form. Here we describe the isolation of two L-ascorbic acid transporters, SVCT1 and SVCT2, from rat complementary DNA libraries, as the first step in investigating the importance of L-ascorbic acid transport in regulating the supply and metabolism of vitamin C. We find that SVCT1 and SVCT2 each mediate concentrative, high-affinity L-ascorbic acid transport that is stereospecific and is driven by the Na+ electrochemical gradient. Despite their close sequence homology and similar functions, the two isoforms of the transporter are discretely distributed: SVCT1 is mainly confined to epithelial systems (intestine, kidney, liver), whereas SVCT2 serves a host of metabolically active cells and specialized tissues in the brain, eye and other organs. 相似文献
75.
76.
Astrid Musnier Domitille Heitzler Thomas Boulo Sophie Tesseraud Guillaume Durand Charlotte Lécureuil Hervé Guillou Anne Poupon Eric Reiter Pascale Crépieux 《Cellular and molecular life sciences : CMLS》2009,66(21):3487-3503
The mechanisms whereby G protein-coupled receptors (GPCR) activate signalling pathways involved in mRNA translation are ill-defined,
in contrast to tyrosine kinase receptors (TKR). We compared a GPCR and a TKR, both endogenously expressed, for their ability
to mediate phosphorylation of 70-kDa ribosomal S6 kinase p70S6K in primary rat Sertoli cells at two developmental stages.
In proliferating cells stimulated with follicle-stimulating hormone (FSH), active p70S6K was phosphorylated on T389 and T421/S424,
through cAMP-dependent kinase (PKA) and phosphatidyl-inositide-3 kinase (PI3K) antagonizing actions. In FSH-stimulated differentiating
cells, active p70S6K was phosphorylated solely on T389, PKA and PI3K independently enhancing its activity. At both developmental
stages, insulin-induced p70S6K regulation was consistent with reported data. Therefore, TKR and GPCR trigger distinct p70S6K
active conformations. p70S6K developmental regulation was formalized in a dynamic mathematical model fitting the data, which
led to experimentally inaccessible predictions on p70S6K phosphorylation rate. 相似文献
77.
78.
Summary It is possible to demonstrate antibodies against casein in the serum by the Ouchterlony technique. It is a simple technique and needs only a small amount of serum. In a few cases we could demonstrate antibodies against casein in sera, in which the hemagglutination-technique did not show positive results. In some cases, however, sera which were positive in hemagglutination-tests gave negative results by the Ouchterlony technique. The possibility is discussed that by the two techniques different kinds of casein-antibodies can be detected.
Für die Durchführung der serologischen Untersuchungen sind wir FräuleinChristine Dyballa und FräuleinIrene v. Schweinichen zu grossem Dank verpflichtet. 相似文献
Für die Durchführung der serologischen Untersuchungen sind wir FräuleinChristine Dyballa und FräuleinIrene v. Schweinichen zu grossem Dank verpflichtet. 相似文献
79.
80.