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101.
Ten pony mares that had developed stallion-like sexual behavior as the result of anabolic steroid treatment (boldenone undecylenate, 0.55 mg/kg intramuscularly (i.m.), once weekly for 12 injections) were evaluated for ability to aid in detecting estrus in cycling mares. In across-the-fence estrus detection trials, androgenized mares failed to elicit signs of estrus or diestrus. In 10-min pasture trials, in which each androgenized mare was placed in a group of 10 cycling mares (six of which were estrous), seven of the 10 androgenized mares elicited estrous behavior from one or two mares. Observations of the 10 androgenized mares among a pasture group of 21 cycling mares indicated that approximately one third of the mares in estrus could be identified on the basis of their response to androgenized mares. 相似文献
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McDonnell MA Abedin MJ Melendez M Platikanova TN Ecklund JR Ahmed K Kelekar A 《The Journal of biological chemistry》2008,283(29):20149-20158
Previous studies from our laboratory had indicated that cytochrome c-independent processing and activation of caspase-9 by caspase-8 contributed to early amplification of the caspase cascade in tumor necrosis factor (TNF)-alpha-treated murine cells. Here we show that murine caspase-9 is phosphorylated by casein kinase 2 (CK2) on a serine near the site of caspase-8 cleavage. CK2 has been shown to regulate cleavage of the pro-apoptotic Bid protein by phosphorylating serine residues near its caspase-8 cleavage site. Similarly, CK2 modification of Ser(348) on caspase-9 appears to render the protease refractory to cleavage by active caspase-8. This phosphorylation did not affect the ability of caspase-9 to autoprocess. Substitution of Ser(348) abolished phosphorylation but not cleavage, and a phospho-site mutant promoted apoptosis in TNF-alpha-treated caspase-9 knock-out mouse embryo fibroblasts. Furthermore, inhibition of CK2 activity and RNA interference-mediated knockdown of the kinase accelerated caspase-9 activation, whereas phosphatase inhibition delayed both caspase-9 activation and death in response to TNF receptor occupation. Taken together, these studies show that TNF receptor cross-linking promotes dephosphorylation of caspase-9, rendering it susceptible to processing by activated caspase-8 protein. Thus, our data suggest that modification of procaspase-9 to protect it from inappropriate cleavage and activation is yet another mechanism by which the oncogenic kinase CK2 promotes survival. 相似文献
105.
Barbora de Courten Michaela Jakubova Maximilian PJ de Courten Ivica Just Kukurova Silvia Vallova Patrik Krumpolec Ladislav Valkovic Timea Kurdiova Davide Garzon Silvia Barbaresi Helena J. Teede Wim Derave Martin Krssak Giancarlo Aldini Jozef Ukropec Barbara Ukropcova 《Obesity (Silver Spring, Md.)》2016,24(5):1027-1034
106.
Deregulated Bcl-2-immunoglobulin transgene expands a resting but responsive immunoglobulin M and D-expressing B-cell population. 总被引:34,自引:1,他引:33 下载免费PDF全文
T J McDonnell G Nunez F M Platt D Hockenberry L London J P McKearn S J Korsmeyer 《Molecular and cellular biology》1990,10(5):1901-1907
We characterized the basis for the follicular lymphoproliferation in transgenic mice bearing a Bcl-2-immunoglobulin (Bcl-2-Ig) minigene representing the t(14;18) of human follicular lymphoma. Discriminatory S1 nuclease protection assays revealed that the Bcl-2-Ig transgene was overexpressed relative to endogenous mouse Bcl-2 in spleen and thymus. Western (immunoblot) analysis demonstrated the overproduction of the human 25-kilodalton Bcl-2 protein, which arose from the transgene, in spleen, thymus, and the expanded B-cell subset. Despite the generalized lymphoid pattern of deregulation, two-color flow cytometry and density gradient centrifugation indicated that the expanded lymphocytes were predominantly small, resting B cells coexpressing B220, immunoglobulin M (IgM), IgD, Ia, and kappa. Cell cycle analysis confirmed that about 97% of these expanded B cells reside in G0/G1. An extensive characterization of transgenic lines revealed a fourfold excess of IgM-IgD-expressing B cells in spleen and dramatically increased numbers in bone marrow. While resting, these cells proliferated in response to lipopolysaccharide and anti-IgM and demonstrated normal B-cell colony formation in soft agar. Moreover, these B cells, which demonstrated an extended survival in vitro even in the absence of stroma, were also resting in G0, yet were capable of proliferative responses. These findings provide consistent evidence that the accumulation of B cells after Bcl-2 overproduction is secondary to prolonged cell survival and not increased cell cycling. This suggests a unique role for Bcl-2 as a proto-oncogene that enhances cell survival independent of promoting cell division. 相似文献
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The ability to predict structure from sequence is particularly important for toxins, virulence factors, allergens, cytokines, and other proteins of public health importance. Many such functions are represented in the parallel beta-helix and beta-trefoil families. A method using pairwise beta-strand interaction probabilities coupled with evolutionary information represented by sequence profiles is developed to tackle these problems for the beta-helix and beta-trefoil folds. The algorithm BetaWrapPro employs a "wrapping" component that may capture folding processes with an initiation stage followed by processive interaction of the sequence with the already-formed motifs. BetaWrapPro outperforms all previous motif recognition programs for these folds, recognizing the beta-helix with 100% sensitivity and 99.7% specificity and the beta-trefoil with 100% sensitivity and 92.5% specificity, in crossvalidation on a database of all nonredundant known positive and negative examples of these fold classes in the PDB. It additionally aligns 88% of residues for the beta-helices and 86% for the beta-trefoils accurately (within four residues of the exact position) to the structural template, which is then used with the side-chain packing program SCWRL to produce 3D structure predictions. One striking result has been the prediction of an unexpected parallel beta-helix structure for a pollen allergen, and its recent confirmation through solution of its structure. A Web server running BetaWrapPro is available and outputs putative PDB-style coordinates for sequences predicted to form the target folds. 相似文献
109.
Kim KS Lu S Cornelius LA Lombardo LJ Borzilleri RM Schroeder GM Sheng C Rovnyak G Crews D Schmidt RJ Williams DK Bhide RS Traeger SC McDonnell PA Mueller L Sheriff S Newitt JA Pudzianowski AT Yang Z Wild R Lee FY Batorsky R Ryder JS Ortega-Nanos M Shen H Gottardis M Roussell DL 《Bioorganic & medicinal chemistry letters》2006,16(15):3937-3942
Synthesis and SAR of substituted pyrrolotriazine-4-one analogues as Eg5 inhibitors are described. Many of these analogues displayed potent inhibitory activities in the Eg5 ATPase and A2780 cell proliferation assays. In addition, pyrrolotriazine-4-one analogue 26 demonstrated in vivo efficacy in an iv P388 murine leukemia model. Both NMR and X-ray crystallographic studies revealed that these analogues bind to an allosteric site on the Eg5 protein. 相似文献
110.
Gaillard S Grasfeder LL Haeffele CL Lobenhofer EK Chu TM Wolfinger R Kazmin D Koves TR Muoio DM Chang CY McDonnell DP 《Molecular cell》2006,24(5):797-803
In the absence of specific high-affinity agonists and antagonists, it has been difficult to define the target genes and biological responses attributable to many of the orphan nuclear receptors (ONRs). Indeed, it appears that many members of this receptor superfamily are not regulated by classical small molecules but rather their activity is controlled by interacting cofactors. Motivated by this finding, we have developed an approach to genetically isolate specific receptor-cofactor pairs in cells, allowing us to define the biological responses attributable to each complex. This is accomplished by using combinatorial peptide phage display to engineer the receptor interacting domain of each cofactor such that it interacts selectively with one nuclear receptor. In this study, we describe the customization of PGC-1alpha and its use to study the biology of the estrogen-related receptor alpha (ERRalpha) in cultured liver cells. 相似文献