全文获取类型
收费全文 | 18818篇 |
免费 | 1774篇 |
国内免费 | 8篇 |
出版年
2024年 | 18篇 |
2023年 | 105篇 |
2022年 | 165篇 |
2021年 | 621篇 |
2020年 | 340篇 |
2019年 | 443篇 |
2018年 | 501篇 |
2017年 | 444篇 |
2016年 | 705篇 |
2015年 | 1172篇 |
2014年 | 1239篇 |
2013年 | 1290篇 |
2012年 | 1767篇 |
2011年 | 1778篇 |
2010年 | 1098篇 |
2009年 | 951篇 |
2008年 | 1229篇 |
2007年 | 1228篇 |
2006年 | 1070篇 |
2005年 | 971篇 |
2004年 | 911篇 |
2003年 | 723篇 |
2002年 | 647篇 |
2001年 | 126篇 |
2000年 | 78篇 |
1999年 | 108篇 |
1998年 | 115篇 |
1997年 | 79篇 |
1996年 | 70篇 |
1995年 | 52篇 |
1994年 | 45篇 |
1993年 | 48篇 |
1992年 | 34篇 |
1991年 | 25篇 |
1990年 | 20篇 |
1989年 | 28篇 |
1988年 | 18篇 |
1987年 | 16篇 |
1986年 | 14篇 |
1985年 | 24篇 |
1984年 | 21篇 |
1983年 | 25篇 |
1982年 | 22篇 |
1981年 | 18篇 |
1980年 | 13篇 |
1979年 | 12篇 |
1978年 | 13篇 |
1976年 | 11篇 |
1963年 | 10篇 |
1960年 | 13篇 |
排序方式: 共有10000条查询结果,搜索用时 31 毫秒
991.
Mahon MJ Cole JA Lederer ED Segre GV 《Molecular endocrinology (Baltimore, Md.)》2003,17(11):2355-2364
The opossum kidney (OK) line displays PTH-mediated activation of adenylyl cyclase and phospholipase C and inhibition of phosphate (Pi) uptake via regulation of the type IIa sodium-phosphate cotransporter, consistent with effects in vivo. OKH cells, a subclone of the OK cell line, robustly activates PTH-mediated activation of adenylyl cyclase, but is defective in PTH-mediated inhibition of sodium-phosphate cotransport and signaling via phospholipase C. Compared with wild-type OK cells, OKH cells express low levels of the Na+/H+ exchanger regulatory factor 1 (NHERF-1). Stable expression of NHERF-1 in OKH cells (OKH-N1) rescues the PTH-mediated inhibition of sodium-phosphate cotransport. NHERF-1 also restores the capacity of 8-bromo-cAMP and forskolin to inhibit Pi uptake, but the PTH dose-response for cAMP accumulation and inhibition of Pi uptake differ by 2 orders of magnitude. NHERF-1, in addition, modestly restores phorbol ester-mediated inhibition of Pi uptake, which is much weaker than that elicited by PTH. A poor correlation exists between the inhibition of Pi uptake mediated by PTH ( approximately 60%) and the inhibition mediated by phorbol 12-myristate 13-acetate ( approximately 30%) and the ability of these molecules to activate the protein kinase C-responsive reporter gene. Furthermore, we show that NHERF-1 directly interacts with type IIa cotransporter in OK cells. Although, PTH-mediated inhibition of Pi uptake in OK cells is largely NHERF-1 dependent, the signaling pathway(s) by which this occurs is still unclear. These pathways may involve cooperativity between cAMP- and protein kinase C-dependent pathways or activation/inhibition of an unrecognized NHERF-1-dependent pathway(s). 相似文献
992.
Spectroscopic methods were used to monitor the unfolding of the leucine specific (LS) and the leucine-isoleucine-valine (LIV) binding proteins. Our studies indicate that ligand-free protein undergoes a simple two-state unfolding, whereas the protein-ligand complex undergoes a three-state unfolding model. Ligand binding causes significant stabilization of both proteins. There is correlation between ligand hydrophobicity and protein stabilization: the most hydrophobic ligand, isoleucine, causes the most significant stabilization of LIV protein. A disulfide bond present in N-domain of both proteins makes a large contribution to the protein stability of these periplasmic binding receptors. 相似文献
993.
994.
995.
996.
Zhu Y Nam J Humara JM Mysore KS Lee LY Cao H Valentine L Li J Kaiser AD Kopecky AL Hwang HH Bhattacharjee S Rao PK Tzfira T Rajagopal J Yi H Veena Yadav BS Crane YM Lin K Larcher Y Gelvin MJ Knue M Ramos C Zhao X Davis SJ Kim SI Ranjith-Kumar CT Choi YJ Hallan VK Chattopadhyay S Sui X Ziemienowicz A Matthysse AG Citovsky V Hohn B Gelvin SB 《Plant physiology》2003,132(2):494-505
Limited knowledge currently exists regarding the roles of plant genes and proteins in the Agrobacterium tumefaciens-mediated transformation process. To understand the host contribution to transformation, we carried out root-based transformation assays to identify Arabidopsis mutants that are resistant to Agrobacterium transformation (rat mutants). To date, we have identified 126 rat mutants by screening libraries of T-DNA insertion mutants and by using various “reverse genetic” approaches. These mutants disrupt expression of genes of numerous categories, including chromatin structural and remodeling genes, and genes encoding proteins implicated in nuclear targeting, cell wall structure and metabolism, cytoskeleton structure and function, and signal transduction. Here, we present an update on the identification and characterization of these rat mutants. 相似文献
997.
By binding SIRPalpha or calreticulin/CD91, lung collectins act as dual function surveillance molecules to suppress or enhance inflammation 总被引:24,自引:0,他引:24
Surfactant proteins A and D (SP-A and SP-D) are lung collectins composed of two regions, a globular head domain that binds PAMPs and a collagenous tail domain that initiates phagocytosis. We provide evidence that SP-A and SP-D act in a dual manner, to enhance or suppress inflammatory mediator production depending on binding orientation. SP-A and SP-D bind SIRPalpha through their globular heads to initiate a signaling pathway that blocks proinflammatory mediator production. In contrast, their collagenous tails stimulate proinflammatory mediator production through binding to calreticulin/CD91. Together a model is implied in which SP-A and SP-D help maintain a non/anti-inflammatory lung environment by stimulating SIRPalpha on resident cells through their globular heads. However, interaction of these heads with PAMPs on foreign organisms or damaged cells and presentation of the collagenous tails in an aggregated state to calreticulin/CD91, stimulates phagocytosis and proinflammatory responses. 相似文献
998.
Prediction of mammalian microRNA targets 总被引:143,自引:0,他引:143
999.
The S. cerevisiae SCF(Cdc4) is a prototype of RING-type SCF E3s, which recruit substrates for polyubiquitination by the Cdc34 ubiquitin-conjugating enzyme. Current models propose that Cdc34 ubiquitinates the substrate while remaining bound to the RING domain. In contrast, we found that the formation of a ubiquitin thiol ester regulates the Cdc34/SCF(Cdc4) binding equilibrium by increasing the dissociation rate constant, with only a minor effect on the association rate. By using a F72VCdc34 mutant with increased affinity for the RING domain, we demonstrate that release of ubiquitin-charged Cdc34-S - Ub from the RING is essential for ubiquitination of the SCF(Cdc4)-bound substrate Sic1. Release of ubiquitin-charged E2 from E3 prior to ubiquitin transfer is a previously unrecognized step in ubiquitination, which can explain both the modification of multiple lysines on the recruited substrate and the extension of polyubiquitin chains. We discuss implications of this finding for function of other ubiquitin ligases. 相似文献
1000.
Wolin MJ Miller TL Collins MD Lawson PA 《Applied and environmental microbiology》2003,69(10):6321-6326
Formate stimulates growth of a new bacterium from human feces. With high formate, it ferments glucose to acetate via the Wood-Ljungdahl pathway. The original isolate fermented vegetable cellulose and carboxymethylcellulose, but it lost this ability after storage at -76 degrees C. 16S rRNA gene sequencing identifies it as a distinct line within the Clostridium coccoides supra-generic rRNA grouping. We propose naming it Bryantella formatexigens gen. nov., sp. nov. 相似文献