全文获取类型
收费全文 | 17264篇 |
免费 | 26篇 |
国内免费 | 67篇 |
专业分类
系统科学 | 123篇 |
丛书文集 | 288篇 |
教育与普及 | 43篇 |
理论与方法论 | 63篇 |
现状及发展 | 7398篇 |
研究方法 | 909篇 |
综合类 | 8270篇 |
自然研究 | 263篇 |
出版年
2013年 | 112篇 |
2012年 | 298篇 |
2011年 | 566篇 |
2010年 | 104篇 |
2009年 | 99篇 |
2008年 | 316篇 |
2007年 | 361篇 |
2006年 | 377篇 |
2005年 | 376篇 |
2004年 | 376篇 |
2003年 | 323篇 |
2002年 | 320篇 |
2001年 | 609篇 |
2000年 | 571篇 |
1999年 | 388篇 |
1992年 | 325篇 |
1991年 | 264篇 |
1990年 | 279篇 |
1989年 | 253篇 |
1988年 | 235篇 |
1987年 | 280篇 |
1986年 | 291篇 |
1985年 | 319篇 |
1984年 | 280篇 |
1983年 | 222篇 |
1982年 | 182篇 |
1981年 | 195篇 |
1980年 | 249篇 |
1979年 | 566篇 |
1978年 | 432篇 |
1977年 | 425篇 |
1976年 | 314篇 |
1975年 | 349篇 |
1974年 | 515篇 |
1973年 | 437篇 |
1972年 | 428篇 |
1971年 | 519篇 |
1970年 | 688篇 |
1969年 | 484篇 |
1968年 | 399篇 |
1967年 | 487篇 |
1966年 | 398篇 |
1965年 | 282篇 |
1959年 | 162篇 |
1958年 | 268篇 |
1957年 | 207篇 |
1956年 | 180篇 |
1955年 | 144篇 |
1954年 | 150篇 |
1948年 | 126篇 |
排序方式: 共有10000条查询结果,搜索用时 31 毫秒
841.
Diversity of structures and properties among catalases 总被引:2,自引:0,他引:2
More than 300 catalase sequences are now available, divided among monofunctional catalases (> 225), bifunctional catalase-peroxidases (> 50) and manganese-containing catalases (> 25). When combined with the recent appearance of crystal structures from at least two representatives from each of these groups (nine from the monofunctional catalases), valuable insights into the catalatic reaction mechanism in its various forms and into catalase evolution have been gained. The structures have revealed an unusually large number of modifications unique to catalases, a result of interacting with reactive oxygen species. Biochemical and physiological characterization of catalases from many different organisms has revealed a surprisingly wide range of catalatic efficiencies, despite similar sequences. Catalase gene expression in micro-organisms generally is controlled either by sensors of reactive oxygen species or by growth phase regulons, although the detailed mechanisms vary considerably.Received 2 June 2003; received after revision 24 June 2003; accepted 1 July 2003 相似文献
842.
843.
844.
Sanchez-Perez I Rodriguez-Hernandez CJ Manguan-García C Torres A Perona R Murguía JR 《Cellular and molecular life sciences : CMLS》2004,61(6):700-708
The immunosuppressants tacrolimus (FK506) and cyclosporin A (CsA) have increased the survival rates in organ transplantation. Both drugs inhibit the protein phosphatase calcineurin (CaN) in activated T cells, exhibiting similar side-effects. Diabetes is observed more often in FK506 than CsA therapy, probably due to inhibition of new molecular targets other than CaN. We studied FK506 toxicity in mammalian cells. FK506, but not CsA, regulated p38 activation by osmotic stress, and decreased viability in osmostressed cells. In addition, FK506 treatment strongly increased the phosphorylation of the eukaryotic initiation factor-2a (eIF-2a) subunit. eIF-2a phosphorylation, p38 inhibition and cell lethality were relieved by addition of excess amino acids to the medium, suggesting that amino acid availability mediated FK506 toxicity. Therefore, these FK506-dependent responses could be relevant to the non-therapeutic effects of FK506 therapy.Received 16 October 2003; received after revision 8 January 2004; accepted 14 January 2004 相似文献
845.
Hoekstra PJ Anderson GM Limburg PC Korf J Kallenberg CG Minderaa RB 《Cellular and molecular life sciences : CMLS》2004,61(7-8):886-898
Tourettes syndrome is a childhood-onset neuropsychiatric disorder characterized by the presence of both multiple motor and vocal tics. While the pathogenesis at a molecular and cellular level remains unknown, structural and functional neuroimaging studies point to the involvement of the basal ganglia and related cortico-striato-thalamo-cortical circuits as the neuroanatomical site for Tourettes syndrome. Moreover, Tourettes syndrome has a strong genetic component, and considerable progress has been made in understanding the mode of transmission and in identifying potential genomic loci. Summaries of recent findings in these areas will be reviewed, followed by a critical overview of findings both supporting and challenging the proposed autoimmune hypothesis of Tourettes syndrome. We conclude that Tourettes syndrome is a heterogeneous disorder, and that immune factors may indeed be involved in some patients.Received 12 August 2003; received after revision 8 October 2003; accepted 31 October 2003 相似文献
846.
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
847.
Ferioli ME Bottone MG Soldani C Pellicciari C 《Cellular and molecular life sciences : CMLS》2004,61(21):2767-2773
The suggestion has been made that polyamines may be involved in the control of cell death, since exceedingly high or low levels induce apoptosis in different cell systems. For a deeper insight into the relationship between apoptosis and polyamine metabolism, we investigated in vitro the effect on rat thymocytes of mitoguazone (MGBG, which inhibits S-adenosylmethionine decarboxylase, i.e. a key enzyme in the polyamine biosynthetic pathway). Thymocytes were selected as an especially suitable model system, since they undergo spontaneous apoptosis in vivo and can be easily induced to apoptose in vitro by etoposide, used here as an apoptogenic agent. MGBG protected thymocytes from both spontaneous and drug-induced apoptosis, and this protective effect was associated with a decrease in polyamine oxidase activity and total polyamine levels.Received 7 July 2004; received after revision 2 September 2004; accepted 9 September 2004 相似文献
848.
Apoptotic cell death in the lactating mammary gland is enhanced by a folding variant of α-lactalbumin 总被引:1,自引:0,他引:1
Apoptosis is essential to eliminate secretory epithelial cells during the involution of the mammary gland. The environmental regulation of this process is however, poorly understood. This study tested the effect of HAMLET (human -lactalbumin made lethal to tumor cells) on mammary cells. Plastic pellets containing HAMLET were implanted into the fourth inguinal mammary gland of lactating mice for 3 days. Exposure of mammary tissue to HAMLET resulted in morphological changes typical for apoptosis and in a stimulation of caspase-3 activity in alveolar epithelial cells near the HAMLET pellets but not more distant to the pellet or in contralateral glands. The effect was specific for HAMLET and no effects were observed when mammary glands were exposed to native a-lactalbumin or fatty acid alone. HAMLET also induced cell death in vitro in a mouse mammary epithelial cell line. The results suggest that HAMLET can mediate apoptotic cell death in mammary gland tissue.Received 30 January 2004; received after revision 5 March 2004; accepted 16 March 2004 相似文献
849.
850.
Mignot C Boespflug-Tanguy O Gelot A Dautigny A Pham-Dinh D Rodriguez D 《Cellular and molecular life sciences : CMLS》2004,61(3):369-385
Alexander disease (AXD) is the first primary astrocytic disorder. This encephalopathy is caused by dominant mutations in the glial fibrillary acidic protein (GFAP) gene, encoding the main intermediate filament of astrocyte. Pathologically, this neurodegenerative disease is characterised by dystrophic astrocytes containing intermediate filament aggregates associated with myelin abnormalities.More than 20 GFAP mutations have been reported. Many of them cluster in highly conserved regions between several intermediate filaments. Contrary to other intermediate filament-related diseases, AXD seems to be the consequence of a toxic gain of function induced by aggregates. This is supported by the phenotype of mice overexpressing human GFAP. Nevertheless, GFAP null mice display myelin abnormalities and blood-brain barrier dysfunction that are present in AXD.Given the pivotal role of astrocytes in brain physiology, there are many possibilities for astrocytes to dysfunction and to impair the functions of other cells. Physiopathological hypotheses are discussed in the frame of AXD.Received 11 April 2003; received after revision 22 July 2003; accepted 31 July 2003Both authors contributed equally to this work. 相似文献