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11.
Erroneous estimates of ingroup relationships can be caused by attributes in the outgroup chosen to root the tree. Phylogenetic analyses of DNA sequences frequently yield incorrect estimates of ingroup relationships when the outgroup used to "root" the tree is highly divergent from the ingroup. This is especially the case when the outgroup has a different base composition than the ingroup. Unfortunately, in many instances, alternative less divergent outgroups are not available. In such cases, investigators must either target genes with attributes that minimize the problem (slowly evolving genes with stationary base compositions--which are often not ideal for estimating relationships among the more closely related ingroup taxa) or use inference models that are explicitly tailored to deal with an attenuated historical signal with a superimposed non-stationary base composition. In this paper we explore the problem both empirically and through simulation. For the empirical component we looked at the phylogenetic relationships among elasmobranch fishes (sharks and rays), a group whose closest living outgroup, the holocephalan Ghost fishes, are separated from the elasmobranchs by more than 100 million years of evolution. We compiled a data set for analysis comprising 10 single-copy nuclear protein-coding genes (12,096 bp) for representatives of the major lineages within elasmobranchs and holocephalans. For the simulation, we used an evolutionary model on a fixed tree topology to generate DNA sequence data sets which varied both in their distance to the outgroup, and in their base compositional difference between ingroup and outgroup. Results from both the empirical data set and the simulation, support the idea that deviation from base compositional stationarity, in conjunction with distance from the root can act in concert to compromise accuracy of estimated relationships within the ingroup. We tested several approaches to mitigate such problems. We found, that excluding genes with overall faster rates and heterogeneous base compositions, while the least sophisticated of the methods evaluated, seemed to be the most effective. 相似文献
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J Klein J Gonzalez J Duchene L Esposito JP Pradère E Neau C Delage D Calise A Ahluwalia P Carayon JB Pesquero M Bader JP Schanstra JL Bascands 《FASEB journal》2009,23(1):134-142
Renal fibrosis is the common histological feature of advanced glomerular and tubulointerstitial disease leading to end-stage renal disease (ESRD). However, specific antifibrotic therapies to slow down the evolution to ESRD are still absent. Because persistent inflammation is a key event in the development of fibrosis, we hypothesized that the proinflammatory kinin B1 receptor (B1R) could be such a new target. Here we show that, in the unilateral ureteral obstruction model of renal fibrosis, the B1R is overexpressed and that delayed treatment with an orally active nonpeptide B1R antagonist blocks macrophage infiltration, leading to a reversal of the level of renal fibrosis. In vivo bone marrow transplantation studies as well as in vitro studies on renal cells show that part of this antifibrotic mechanism of B1R blockade involves a direct effect on resident renal cells by inhibiting chemokine CCL2 and CCL7 expression. These findings suggest that blocking the B1R is a promising antifibrotic therapy. 相似文献
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Hoard-Fruchey HM Goetzman E Benson L Naylor S Vockley J 《The Journal of biological chemistry》2004,279(14):13786-13791
Microelectrospray ionization-mass spectrometry was used to directly observe electron transferring flavoprotein.flavoprotein dehydrogenase interactions. When electron transferring flavoprotein and porcine dimethylglycine dehydrogenase or sarcosine dehydrogenase were incubated together in the absence of substrate, a relative molecular mass corresponding to the flavoprotein.electron transferring flavoprotein complex was observed, providing the first direct observation of these mammalian complexes. When an acyl-CoA dehydrogenase family member, human short chain acyl-CoA dehydrogenase, was incubated with dimethylglycine dehydrogenase and electron transferring flavoprotein, the microelectrospray ionization-mass spectrometry signal for the dimethylglycine dehydrogenase.electron transferring flavoprotein complex decreased, indicating that the acyl-CoA dehydrogenases have the ability to compete with the dimethylglycine dehydrogenase/sarcosine dehydrogenase family for access to electron transferring flavoprotein. Surface plasmon resonance solution competition experiments revealed affinity constants of 2.0 and 5.0 microm for the dimethylglycine dehydrogenase-electron transferring flavoprotein and short chain acyl-CoA dehydrogenase-electron transferring flavoprotein interactions, respectively, suggesting the same or closely overlapping binding motif(s) on electron transferring flavoprotein for dehydrogenase interaction. 相似文献
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Riera KM Rothfusz NE Wilusz RE Weinberg JB Guilak F McNulty AL 《Arthritis research & therapy》2011,13(6):R187
Introduction
Interleukin-1 (IL-1) and tumor necrosis factor-α (TNF-α) are up-regulated in injured and osteoarthritic knee joints. IL-1 and TNF-α inhibit integrative meniscal repair; however, the mechanisms by which this inhibition occurs are not fully understood. Transforming growth factor-β1 (TGF-β1) increases meniscal cell proliferation and accumulation, and enhances integrative meniscal repair. An improved understanding of the mechanisms modulating meniscal cell proliferation and migration will help to improve approaches for enhancing intrinsic or tissue-engineered repair of the meniscus. The goal of this study was to examine the hypothesis that IL-1 and TNF-α suppress, while TGF-β1 enhances, cellular proliferation and migration in cell and tissue models of meniscal repair. 相似文献19.
Riazi MA Brinkman-Mills P Johnson A Naylor SL Minoshima S Shimizu N Baldini A McDermid HE 《Genomics》1999,62(1):90-94
Duplication of a segment of the long arm of human chromosome 3 (3q26.3-q27) results in a syndrome characterized by multiple congenital abnormalities and neurological anomalies in some patients. We have identified a novel gene (KCNMB3) that maps to this region. KCNMB3 has significant sequence similarity to the regulatory subunit of the large-conductance calcium-activated potassium channel. Due to the significance of potassium channels in neuronal functions, the overexpression of this gene may play a role in the abnormal neurological functions seen in some of these patients. A related sequence corresponding to the second and third exons of this gene resides in the pericentromeric region of 22q11, where a number of other unprocessed pseudogenes are known to map. 相似文献
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