全文获取类型
收费全文 | 69840篇 |
免费 | 6486篇 |
国内免费 | 24篇 |
出版年
2023年 | 279篇 |
2022年 | 556篇 |
2021年 | 1104篇 |
2020年 | 731篇 |
2019年 | 907篇 |
2018年 | 1212篇 |
2017年 | 1111篇 |
2016年 | 1759篇 |
2015年 | 2735篇 |
2014年 | 3054篇 |
2013年 | 3694篇 |
2012年 | 4994篇 |
2011年 | 4961篇 |
2010年 | 3057篇 |
2009年 | 2677篇 |
2008年 | 4057篇 |
2007年 | 4151篇 |
2006年 | 3871篇 |
2005年 | 3648篇 |
2004年 | 3526篇 |
2003年 | 3260篇 |
2002年 | 3143篇 |
2001年 | 1169篇 |
2000年 | 1020篇 |
1999年 | 967篇 |
1998年 | 950篇 |
1997年 | 666篇 |
1996年 | 604篇 |
1995年 | 547篇 |
1994年 | 575篇 |
1993年 | 571篇 |
1992年 | 684篇 |
1991年 | 561篇 |
1990年 | 548篇 |
1989年 | 541篇 |
1988年 | 489篇 |
1987年 | 448篇 |
1986年 | 456篇 |
1985年 | 430篇 |
1984年 | 494篇 |
1983年 | 458篇 |
1982年 | 479篇 |
1981年 | 439篇 |
1980年 | 456篇 |
1979年 | 365篇 |
1978年 | 347篇 |
1977年 | 316篇 |
1976年 | 300篇 |
1974年 | 261篇 |
1973年 | 235篇 |
排序方式: 共有10000条查询结果,搜索用时 31 毫秒
991.
Regulation of epidermin biosynthetic genes by EpiQ 总被引:14,自引:1,他引:13
992.
Isolation and properties of a soluble sialidase from the culture fluid of Chinese hamster ovary cells 总被引:3,自引:1,他引:2
Warner Thomas G.; Chang Joseph; Ferrari Jeff; Harris Reed; McNerney Thomas; Bennett Greg; Burnier John; Sliwkowski Mary B. 《Glycobiology》1993,3(5):455-463
A Soluble sialidase that can degrade recombinant glycoproteinsexpressed in Chinese hamster ovary (CHO) cells has been isolatedand purified to near homogeneity from the cell culture fluidof this host. Purification of 相似文献
993.
Low-sulphated oligosaccharides derived from heparan sulphate inhibit normal angiogenesis 总被引:1,自引:0,他引:1
Hahnenberger Rudolph; Jakobson ke M.; Ansari Akbar; Wehler Thomas; Svahn Carl Magnus; Lindahl Ulf 《Glycobiology》1993,3(6):567-573
Heparin, with or without the addition of an adrenocorticosteroid,can inhibit normal angiogenesis in the chick embryo chorioallantoicmembrane. Low- or non-sulphated heparin fragments also haveanti-angiogenic effect. Attempts to define a saccharide structureresponsible for the anti-angiogenic effect implicated a -[GlcAß1,4-GlcNAc 相似文献
994.
Yue Zhou Lynn P. Chorich Virendra B. Mahesh Thomas F. Ogle 《The Journal of steroid biochemistry and molecular biology》1993,46(6):687-698
The objective of this study was to examine the mechanisms of estrogen receptor (ER) processing and replenishment in the uterus of ovariectomized rats after estradiol and progesterone treatment. Uterine ER binding activity, ER protein and ER mRNA were measured by receptor binding exchange assay, Western blot and slot blot, respectively. The regulation of ER levels in rat uterus by estradiol and progesterone was very dramatic. Changes in ER protein were faithfully reflected by changes in binding activity. Estradiol caused receptor “processing” within 4 h of administration followed by recovery or “replenishment” of ER levels to the initial level by 20 h. The term “processing” has previously been used to describe the loss of ER binding activity in the early phase of estradiol-action, but it was never clear whether the ligand binding site was inactivated by processing or if the receptor molecule actually disappeared. This study shows that receptor “processing” constitutes disappearance of receptor protein and the later “replenishment” phase represents new ER protein rather than recycling of “processed” receptor. Progesterone-action, on the other hand, influenced only the “replenishment” phase by blocking recovery of ER protein. ER mRNA was suppressed by estradiol at 8 h, after the receptor was “processed” and “replenishment” already initiated. Progesterone, on the other hand, did not alter the steady state level of the message. Other mechanisms, such as regulation of translation rate of existing mRNA and changes in the rate of degradation of ER proteins are more likely involved in acute regulation of ER by these ovarian steroid hormones. 相似文献
995.
Michael A. Poss Joyce A. Reid Charles A. Free W. Lynn Rogers Helen Weber Denis E. Ryono Tamara Dejneka Jack M. DeForrest Thomas L. Waldron Russell J. Brittain Harold N. Weller Maria P. Cimarusti Edward W. Petrillo 《Bioorganic & medicinal chemistry letters》1993,3(12):2739-2744
The syntheses and pharmacological activity of a series of diol sulfonamides which function as inhibitors of human renin are described. The most potent compound in this series, compound 20 (SQ 33,800), is a subnanomolar inhibitor of human renin (IC50 = 0.35 × 10−9 M). 相似文献
996.
Thomas Kinateder Lukas Drexler Kristina Straub Rainer Merkl Reinhard Sterner 《Protein science : a publication of the Protein Society》2023,32(1):e4536
The conservation of fold and chemistry of the enzymes associated with histidine biosynthesis suggests that this pathway evolved prior to the diversification of Bacteria, Archaea, and Eukaryotes. The only exception is the histidinol phosphate phosphatase (HolPase). So far, non-homologous HolPases that possess distinct folds and belong to three different protein superfamilies have been identified in various phylogenetic clades. However, their evolution has remained unknown to date. Here, we analyzed the evolutionary history of the HolPase from γ-Proteobacteria (HisB-N). It has been argued that HisB-N and its closest homologue d -glycero-d -manno-heptose-1,7-bisphosphate 7-phosphatase (GmhB) have emerged from the same promiscuous ancestral phosphatase. GmhB variants catalyze the hydrolysis of the anomeric d -glycero-d -manno-heptose-1,7-bisphosphate (αHBP or βHBP) with a strong preference for one anomer (αGmhB or βGmhB). We found that HisB-N from Escherichia coli shows promiscuous activity for βHBP but not αHBP, while βGmhB from Crassaminicella sp. shows promiscuous activity for HolP. Accordingly, a combined phylogenetic tree of αGmhBs, βGmhBs, and HisB-N sequences revealed that HisB-Ns form a compact subcluster derived from βGmhBs. Ancestral sequence reconstruction and in vitro analysis revealed a promiscuous HolPase activity in the resurrected enzymes prior to functional divergence of the successors. The following increase in catalytic efficiency of the HolP turnover is reflected in the shape and electrostatics of the active site predicted by AlphaFold. An analysis of the phylogenetic tree led to a revised evolutionary model that proposes the horizontal gene transfer of a promiscuous βGmhB from δ- to γ-Proteobacteria where it evolved to the modern HisB-N. 相似文献
997.
Hannah Maus Gerald Hinze Stefan Josef Hammerschmidt Thomas Basché Tanja Schirmeister 《Protein science : a publication of the Protein Society》2023,32(1):e4526
Ligand binding to proteins often is accompanied by conformational transitions. Here, we describe a competition assay based on single molecule Förster resonance energy transfer (smFRET) to investigate the ligand-induced conformational changes of the dengue virus (DENV) NS2B-NS3 protease, which can adopt at least two different conformations. First, a competitive ligand was used to stabilize the closed conformation of the protease. Subsequent addition of the allosteric inhibitor reduced the fraction of the closed conformation and simultaneously increased the fraction of the open conformation, demonstrating that the allosteric inhibitor stabilizes the open conformation. In addition, the proportions of open and closed conformations at different concentrations of the allosteric inhibitor were used to determine its binding affinity to the protease. The KD value observed is in accordance with the IC50 determined in the fluorometric assay. Our novel approach appears to be a valuable tool to study conformational transitions of other proteases and enzymes. 相似文献
998.
Summary Population dynamics of the epizoic bivalve Lissarca notorcadensis living on spines of cidaroid sea urchins in the Weddell Sea were investigated. Total production (somatic & gonad) of the suspension feeding bivalve ranged between 16.5 and 487.4 mg AFDM y–1 per sea urchin. Annual sedimentation rates are not sufficient to maintain the production of the Lissarca sub-populations carried by the sea urchins, and resuspension of organic matter is most likely to be an important food source. The ratio of the number of freshly settled juveniles to the number of embryos brooded is between 0.054 and 0.207 and seems negatively related to the biomass already present, indicating intraspecific competition for space. Interspecific competition for space is caused by the strong preference of L. notorcadensis as well as other epizoa (colonial anthozoans and bryozoans) for the spines located on the aboral hemispere of the sea urchins.AWI Publication No. 572 相似文献
999.
1000.
Analyses of biomedical studies often necessitate modeling longitudinal causal effects. The current focus on personalized medicine and effect heterogeneity makes this task even more challenging. Toward this end, structural nested mean models (SNMMs) are fundamental tools for studying heterogeneous treatment effects in longitudinal studies. However, when outcomes are binary, current methods for estimating multiplicative and additive SNMM parameters suffer from variation dependence between the causal parameters and the noncausal nuisance parameters. This leads to a series of difficulties in interpretation, estimation, and computation. These difficulties have hindered the uptake of SNMMs in biomedical practice, where binary outcomes are very common. We solve the variation dependence problem for the binary multiplicative SNMM via a reparameterization of the noncausal nuisance parameters. Our novel nuisance parameters are variation independent of the causal parameters, and hence allow for coherent modeling of heterogeneous effects from longitudinal studies with binary outcomes. Our parameterization also provides a key building block for flexible doubly robust estimation of the causal parameters. Along the way, we prove that an additive SNMM with binary outcomes does not admit a variation independent parameterization, thereby justifying the restriction to multiplicative SNMMs. 相似文献