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71.
Peripheral disruption of the Grb10 gene enhances insulin signaling and sensitivity in vivo 总被引:1,自引:0,他引:1 下载免费PDF全文
Wang L Balas B Christ-Roberts CY Kim RY Ramos FJ Kikani CK Li C Deng C Reyna S Musi N Dong LQ DeFronzo RA Liu F 《Molecular and cellular biology》2007,27(18):6497-6505
Grb10 is a pleckstrin homology and Src homology 2 domain-containing protein that interacts with a number of phosphorylated receptor tyrosine kinases, including the insulin receptor. In mice, Grb10 gene expression is imprinted with maternal expression in all tissues except the brain. While the interaction between Grb10 and the insulin receptor has been extensively investigated in cultured cells, whether this adaptor protein plays a positive or negative role in insulin signaling and action remains controversial. In order to investigate the in vivo role of Grb10 in insulin signaling and action in the periphery, we generated Grb10 knockout mice by the gene trap technique and analyzed mice with maternal inheritance of the knockout allele. Disruption of Grb10 gene expression in peripheral tissues had no significant effect on fasting glucose and insulin levels. On the other hand, peripheral-tissue-specific knockout of Grb10 led to significant overgrowth of the mice, consistent with a role for endogenous Grb10 as a growth suppressor. Loss of Grb10 expression in insulin target tissues, such as skeletal muscle and fat, resulted in enhanced insulin-stimulated Akt and mitogen-activated protein kinase phosphorylation. Hyperinsulinemic-euglycemic clamp studies revealed that disruption of Grb10 gene expression in peripheral tissues led to increased insulin sensitivity. Taken together, our results provide strong evidence that Grb10 is a negative regulator of insulin signaling and action in vivo. 相似文献
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Katayama H Sasai K Czerniak BA Carter JL Sen S 《Journal of cellular biochemistry》2007,102(5):1318-1331
Aurora-A is an oncogenic kinase that plays essential roles in mitosis as well as cell survival. Aurora-A interacting protein (AIP) was identified as a negative regulator of Aurora-A with its ectopic over expression inducing destabilization of Aurora-A protein. Here we present evidence that in human cells, contrary to the earlier report, AIP functions in stabilizing rather than destabilizing Aurora-A. Furthermore, AIP is phosphorylated on Serine 70 by Aurora-A but not Aurora-B and expression of phosphorylation mimic mutant of AIP results in prolonged protein stability compared to unphosphorylatable mutant. We observed that when co-expressed with AIP, protein levels of both Aurora-A and Aurora-B are markedly elevated regardless of their kinase activities and phosphorylation state of AIP. Interaction of Aurora kinases with AIP is necessary for this elevated stability. This phenomenon is commonly detected in several human cancer cell lines used in this study. Depletion of AIP by RNA interference decreased Aurora-A but not Aurora-B in two of the three cell lines analyzed, indicating that under physiological condition, AIP functions in stabilization of Aurora-A but not Aurora-B, though this regulation may be dependent on additional factors as well. Further, AIP siRNA induced cell cycle arrest at G2/M, which is consistent with anticipated loss of function of Aurora-A in these cells. Thus, our study provides the first evidence of a role for AIP in G2/M cell cycle progression by cooperatively regulating protein stabilization of its up-stream regulator, Aurora-A kinase through protein-protein interaction as well as protein phosphorylation. 相似文献
74.
Huiping Zhu Robert M Cabrera Bogdan J Wlodarczyk Daniel Bozinov Deli Wang Robert J Schwartz Richard H Finnell 《BMC developmental biology》2007,7(1):128
Background
Heart anomalies are the most frequently observed among all human congenital defects. As with the situation for neural tube defects (NTDs), it has been demonstrated that women who use multivitamins containing folic acid peri-conceptionally have a reduced risk for delivering offspring with conotruncal heart defects [1–3]. Cellular folate transport is mediated by a receptor or binding protein and by an anionic transporter protein system. Defective function of the Folr1 (also known as Folbp1; homologue of human FRα) gene in mice results in inadequate transport, accumulation, or metabolism of folate during cardiovascular morphogenesis. 相似文献75.
Two molecular cytogenetics methods, PRINS (primed in situ DNA labeling) and C-PRINS (cycling PRINS), were optimized for the physical mapping of several types of DNA sequences on the
mitotic chromosomes of the narrow-leafed lupin (Lupinus angustifolius L.). The fragment of the FokI element from Vicia faba was localised by indirect PRINS reaction. Two other sequences, fragments of the coding sequences of L. luteus and of L. angustifolius, were localised by indirect C-PRINS. These techniques are faster and more sensitive than FISH, and they allowed the mapping
of short DNA fragments. The data obtained shows that both types of PRINS are valuable tools for chromosome identification
in lupin. 相似文献
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Sensitivity Analysis of Environmental Process Modeling in a Life Cycle Context: A Case Study of Hemp Crop Production 下载免费PDF全文
Andrianandraina Anne Ventura Tristan Senga Kiessé Bogdan Cazacliu Rachida Idir Hayo M. G. van der Werf 《Journal of Industrial Ecology》2015,19(6):978-993
The aim of this article is to develop a methodological approach allowing to assess the influence of parameters of one or more elementary processes in the foreground system, on the outcomes of a life cycle assessment (LCA) study. From this perspective, the method must be able to: (1) include foreground process modeling in order to avoid the assumption of proportionality between inventory data and reference flows; (2) quantify influences of foreground processes’ parameters (and, possibly, interactions between parameters); and (3) identify trends (either increasing or decreasing) for each parameter on each indicator in order to determine the most favorable direction for parametric variation. These objectives can be reached by combining foreground system modeling, a set of two different sensitivity analysis methods (each one providing different and complementary information), and LCA. The proposed method is applied to a case study of hemp‐based insulation materials for buildings. The present study will focus on the agricultural stage as a foreground system and as a first step encompassing the entire life cycle. A set of technological recommendations were identified for hemp farmers in order to reduce the crop's environmental impacts (from –11% to –89% according to the considered impact category). One of the main limitations of the approach is the need for a detailed model of the foreground process. Further, the method is, at present, rather time‐consuming. However, it offers long‐term advantages given that the higher level of model detail adds robustness to the LCA results. 相似文献
79.
Drivers of temporal changes in temperate forest plant diversity vary across spatial scales 下载免费PDF全文
Markus Bernhardt‐Römermann Lander Baeten Dylan Craven Pieter De Frenne Radim Hédl Jonathan Lenoir Didier Bert Jörg Brunet Markéta Chudomelová Guillaume Decocq Hartmut Dierschke Thomas Dirnböck Inken Dörfler Thilo Heinken Martin Hermy Patrick Hommel Bogdan Jaroszewicz Andrzej Keczyński Daniel L. Kelly Keith J. Kirby Martin Kopecký Martin Macek František Máliš Michael Mirtl Fraser J.G. Mitchell Tobias Naaf Miles Newman George Peterken Petr Petřík Wolfgang Schmidt Tibor Standovár Zoltán Tóth Hans Van Calster Gorik Verstraeten Jozef Vladovič Ondřej Vild Monika Wulf Kris Verheyen 《Global Change Biology》2015,21(10):3726-3737
Global biodiversity is affected by numerous environmental drivers. Yet, the extent to which global environmental changes contribute to changes in local diversity is poorly understood. We investigated biodiversity changes in a meta‐analysis of 39 resurvey studies in European temperate forests (3988 vegetation records in total, 17–75 years between the two surveys) by assessing the importance of (i) coarse‐resolution (i.e., among sites) vs. fine‐resolution (i.e., within sites) environmental differences and (ii) changing environmental conditions between surveys. Our results clarify the mechanisms underlying the direction and magnitude of local‐scale biodiversity changes. While not detecting any net local diversity loss, we observed considerable among‐site variation, partly explained by temporal changes in light availability (a local driver) and density of large herbivores (a regional driver). Furthermore, strong evidence was found that presurvey levels of nitrogen deposition determined subsequent diversity changes. We conclude that models forecasting future biodiversity changes should consider coarse‐resolution environmental changes, account for differences in baseline environmental conditions and for local changes in fine‐resolution environmental conditions. 相似文献
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