全文获取类型
收费全文 | 8146篇 |
免费 | 89篇 |
国内免费 | 58篇 |
专业分类
系统科学 | 50篇 |
丛书文集 | 90篇 |
教育与普及 | 14篇 |
理论与方法论 | 26篇 |
现状及发展 | 3456篇 |
研究方法 | 493篇 |
综合类 | 4058篇 |
自然研究 | 106篇 |
出版年
2016年 | 59篇 |
2014年 | 57篇 |
2013年 | 54篇 |
2012年 | 134篇 |
2011年 | 259篇 |
2010年 | 68篇 |
2009年 | 65篇 |
2008年 | 188篇 |
2007年 | 202篇 |
2006年 | 177篇 |
2005年 | 173篇 |
2004年 | 276篇 |
2003年 | 151篇 |
2002年 | 167篇 |
2001年 | 304篇 |
2000年 | 307篇 |
1999年 | 222篇 |
1992年 | 118篇 |
1991年 | 124篇 |
1990年 | 106篇 |
1989年 | 99篇 |
1988年 | 106篇 |
1987年 | 121篇 |
1986年 | 114篇 |
1985年 | 158篇 |
1984年 | 121篇 |
1983年 | 98篇 |
1982年 | 85篇 |
1981年 | 116篇 |
1980年 | 113篇 |
1979年 | 253篇 |
1978年 | 203篇 |
1977年 | 185篇 |
1976年 | 137篇 |
1975年 | 159篇 |
1974年 | 209篇 |
1973年 | 177篇 |
1972年 | 193篇 |
1971年 | 212篇 |
1970年 | 275篇 |
1969年 | 210篇 |
1968年 | 189篇 |
1967年 | 210篇 |
1966年 | 183篇 |
1965年 | 145篇 |
1959年 | 54篇 |
1958年 | 104篇 |
1957年 | 76篇 |
1956年 | 73篇 |
1954年 | 74篇 |
排序方式: 共有8293条查询结果,搜索用时 125 毫秒
421.
422.
Page NM 《Cellular and molecular life sciences : CMLS》2004,61(13):1652-1663
The mammalian tachykinins are a family of peptides that, until recently, has included substance P (SP), neurokinin A and neurokinin B. Since, the discovery of a third preprotachykinin gene (TAC4), the number of tachykinins has more than doubled to reveal several species-divergent peptides. This group includes hemokinin-1 (HK-1) in mouse and rat, endokinin-1 (EK-1) in rabbit, and EKA, EKB, human HK-1 (hHK-1) and hHK(4–11) in humans. Each exhibits a remarkable selectivity and potency for the tachykinin NK1 receptor similar to SP. Their peripheral expression has led to the proposal that they are the endogenous peripheral SP-like endocrine/paracrine agonists where SP is not expressed. Moreover, their strong cross-reactivity with a specific SP antibody leads us to question many of the proposed locations and roles of SP in the periphery. Additionally, three orphan tachykinin gene-related peptides are identified on TAC4, in rabbit, EK-2 and in humans, EKC and EKD.Received 25 January 2004; received after revision 18 February 2004; accepted 27 February 2004 相似文献
423.
Ubiquitin-proteasome pathway as a primary defender against TRAIL-mediated cell death 总被引:3,自引:0,他引:3
Kim S Choi K Kwon D Benveniste EN Choi C 《Cellular and molecular life sciences : CMLS》2004,61(9):1075-1081
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptotic cell death as well as expression of proinflammatory genes such as CXCL8 in malignant human astrocytoma cells. However, the molecular mechanisms that determine the fate of cells are not yet understood. The ubiquitin (Ub)-proteasome pathway regulates a wide range of cellular functions through degradation of various regulatory proteins; given this, we hypothesized that this pathway may play a central role in TRAIL-mediated signaling. We demonstrate here that inhibition of the Ub-proteasome pathway enhanced TRAIL-mediated cell death of human astrocytoma CRT-MG cells within hours by blocking degradation of active caspase-8 and -3. Proteasome inhibitors suppressed TRAIL-mediated activation of NF-B; however, inhibition of the NF-B pathway alone was not sufficient to enhance TRAIL-mediated cell death. Collectively, these results suggest that the Ub-proteasome pathway may play an important role as an antiapoptotic surveillance system by eliminating activated caspases as well as mediating NF-B-dependent signals.Received 30 December 2003; received after revision 9 February 2004; accepted 13 February 2004 相似文献
424.
425.
Smith NJ Chan HW Osborne JE Thomas WG Hannan RD 《Cellular and molecular life sciences : CMLS》2004,61(21):2695-2703
Activation of the type 1 angiotensin II receptor (AT(1)R) is associated with the aetiology of left ventricular hypertrophy, although the exact intracellular signalling mechanism(s) remain unclear. Transactivation of the epidermal growth factor receptor (EGFR) has emerged as a central mechanism by which the G protein-coupled AT(1)R, which lacks intrinsic tyrosine kinase activity, can stimulate the mitogen-activated protein kinase signalling pathways thought to mediate cardiac hypertrophy. Current studies support a model whereby AT(1)R-dependent transactivation of EGFRs on cardiomyocytes involves stimulation of membrane-bound metalloproteases, which in turn cleave EGFR ligands such as heparin-binding EGF from a plasma membrane-associated precursor. Numerous aspects of the 'triple membrane-passing signalling' paradigm of AT(1)R-induced EGFR transactivation remain to be characterised, including the identity of the specific metalloproteases involved, the intracellular mechanism for their activation and the exact EGFR subtypes required. Here we examine how 'hijacking' of the EGFR might explain the ability of the AT(1)R to elicit the temporally and qualitatively diverse responses characteristic of the hypertrophic phenotype, and discuss the ramifications of delineating these pathways for the development of new therapeutic strategies to combat cardiac hypertrophy. 相似文献
426.
DNA damage repair and transcription 总被引:2,自引:0,他引:2
427.
Gelsolin superfamily proteins: key regulators of cellular functions 总被引:10,自引:0,他引:10
Silacci P Mazzolai L Gauci C Stergiopulos N Yin HL Hayoz D 《Cellular and molecular life sciences : CMLS》2004,61(19-20):2614-2623
Cytoskeletal rearrangement occurs in a variety of cellular processes and involves a wide spectrum of proteins. Among these, the gelsolin superfamily proteins control actin organization by severing filaments, capping filament ends and nucleating actin assembly [1]. Gelsolin is the founding member of this family, which now contains at least another six members: villin, adseverin, capG, advillin, supervillin and flightless I. In addition to their respective role in actin filament remodeling, these proteins have some specific and apparently non-overlapping particular roles in several cellular processes, including cell motility, control of apoptosis and regulation of phagocytosis (summarized in table 1). Evidence suggests that proteins belonging to the gelsolin superfamily may be involved in other processes, including gene expression regulation. This review will focus on some of the known functions of the gelsolin superfamily proteins, thus providing a basis for reflection on other possible and as yet incompletely understood roles for these proteins. 相似文献
428.
Gbaguidi B Mazurkiewicz P Konings WN Driessen AJ Ruysschaert JM Vigano C 《Cellular and molecular life sciences : CMLS》2004,61(19-20):2646-2657
LmrP from Lactococcus lactis is a 45-kDa membrane protein that confers resistance to a wide variety of lipophilic compounds by acting as a proton motive force-driven efflux pump. This study shows that both the proton motive force and ligand interaction alter the accessibility of cytosolic tryptophan residues to a hydrophilic quencher. The proton motive force mediates an increase of LmrP accessibility toward the external medium and results in higher drug binding. Residues Asp128 and Asp68, from cytosolic loops, are involved in the proton motive force-mediated accessibility change. Ligand binding does not modify the protein accessibility, but the proton motive force-mediated restructuring is prerequisite for a subsequent accessibility change mediated by ligand binding. Asp142 cooperates with other membrane-embedded carboxylic residues to promote a conformational change that increases LmrP accessibility toward the hydrophilic quencher. This drug binding-mediated reorganization may be related to the transition between the high- and low-affinity drug-binding sites and is crucial for drug release in the extracellular medium. 相似文献
429.
RASSF1A, the new guardian of mitosis 总被引:3,自引:0,他引:3
Máthé E 《Nature genetics》2004,36(2):117-118
430.
Essential role of Plzf in maintenance of spermatogonial stem cells 总被引:15,自引:0,他引:15
Costoya JA Hobbs RM Barna M Cattoretti G Manova K Sukhwani M Orwig KE Wolgemuth DJ Pandolfi PP 《Nature genetics》2004,36(6):653-659