全文获取类型
收费全文 | 4512篇 |
免费 | 21篇 |
国内免费 | 65篇 |
专业分类
系统科学 | 28篇 |
丛书文集 | 83篇 |
教育与普及 | 64篇 |
理论与方法论 | 5篇 |
现状及发展 | 2006篇 |
研究方法 | 216篇 |
综合类 | 2183篇 |
自然研究 | 13篇 |
出版年
2018年 | 40篇 |
2017年 | 30篇 |
2012年 | 62篇 |
2011年 | 90篇 |
2010年 | 38篇 |
2009年 | 104篇 |
2008年 | 91篇 |
2007年 | 123篇 |
2006年 | 84篇 |
2005年 | 120篇 |
2004年 | 134篇 |
2003年 | 88篇 |
2002年 | 85篇 |
2001年 | 221篇 |
2000年 | 195篇 |
1999年 | 143篇 |
1998年 | 32篇 |
1997年 | 28篇 |
1995年 | 32篇 |
1992年 | 101篇 |
1991年 | 90篇 |
1990年 | 98篇 |
1989年 | 71篇 |
1988年 | 79篇 |
1987年 | 81篇 |
1986年 | 59篇 |
1985年 | 101篇 |
1984年 | 81篇 |
1983年 | 62篇 |
1982年 | 66篇 |
1981年 | 59篇 |
1980年 | 75篇 |
1979年 | 148篇 |
1978年 | 138篇 |
1977年 | 109篇 |
1976年 | 79篇 |
1975年 | 73篇 |
1974年 | 98篇 |
1973年 | 104篇 |
1972年 | 89篇 |
1971年 | 115篇 |
1970年 | 101篇 |
1969年 | 98篇 |
1968年 | 100篇 |
1967年 | 89篇 |
1966年 | 86篇 |
1965年 | 59篇 |
1958年 | 42篇 |
1957年 | 32篇 |
1956年 | 29篇 |
排序方式: 共有4598条查询结果,搜索用时 15 毫秒
91.
A. Fridkin A. Penkner V. Jantsch Y. Gruenbaum 《Cellular and molecular life sciences : CMLS》2009,66(9):1518-1533
92.
J. Kim D. C. Han J. M. Kim S. Y. Lee S. J. Kim J. R. Woo J. W. Lee S.-K. Jung K. S. Yoon H. G. Cheon S. S. Kim S. H. Hong B.-M. Kwon 《Cellular and molecular life sciences : CMLS》2009,66(10):1766-1781
Indenone KR-62776 acts as an agonist of PPARγ without inducing obesity in animal models and cells. X-ray crystallography reveals
that the indenone occupies the binding pocket in a different manner than rosiglitazone. 2-Dimensional gel-electrophoresis
showed that the expression of 42 proteins was altered more than 2.0-fold between KR-62776- or rosiglitazone-treated adipocyte
cells and control cells. Rosiglitazone down-regulated the expression of ERK1/2 and suppressed the phosphorylation of ERK1/2
in these cells. However, the expression of ERK1/2 was up-regulated in KR-62776-treated cells. Phosphorylated ERK1/2, activated
by indenone, affects the localization of PPARγ, suggesting a mechanism for indenone-inhibition of adipogenesis in 3T3-L1 preadipocyte
cells. The preadipocyte cells are treated with ERK1/2 inhibitor PD98059, a large amount of the cells are converted to adipocyte
cells. These results support the conclusion that the localization of PPARγ is one of the key factors explaining the biological
responses of the ligands.
Received 04 March 2009; received after revision 13 March 2009; accepted 17 March 2009 相似文献
93.
Huet J Wyckmans J Wintjens R Boussard P Raussens V Vandenbussche G Ruysschaert JM Azarkan M Looze Y 《Cellular and molecular life sciences : CMLS》2006,63(24):3042-3054
Two chitinases, able to use tetra-N-acetylglucosamine, chitin and chitosan as substrates, were characterized after purification from Carica papaya latex. The complete amino acid sequence of the major form and about 40% of the minor one were determined through proteolytic
digestions and mass spectroscopy analysis. Sequencing demonstrated that both papaya chitinases are members of the family 19
of glycosyl hydrolases (GH19). Based on the known 3-D structures of other members of family GH19, it was expected that papaya
chitinases would adopt all-alpha structures. However, circular dichroism and infrared spectroscopy indicated, for the papaya
chitinases, a content of 15–20% of extended structures besides the expected 40% of alpha helices. Since the fully sequenced
papaya chitinase contains a large number of proline residues the possibility that papaya chitinase contains polyproline II
stretches was examined in the context of their resistance against proteolytic degradation.
Received 11 July 2006; received after revision 13 October 2006; accepted 25 October 2006 相似文献
94.
Birnbaum RY Zvulunov A Hallel-Halevy D Cagnano E Finer G Ofir R Geiger D Silberstein E Feferman Y Birk OS 《Nature genetics》2006,38(7):749-751
We describe an Israeli Jewish Moroccan family presenting with autosomal dominant seborrhea-like dermatosis with psoriasiform elements, including enhanced keratinocyte proliferation, parakeratosis, follicular plugging, Pityrosporum ovale overgrowth and dermal CD4 lymphocyte infiltrate. We mapped the disease gene to a 0.5-cM region overlapping the PSORS2 locus (17q25) and identified a frameshift mutation in ZNF750, which encodes a putative C2H2 zinc finger protein. ZNF750 is normally expressed in keratinocytes but not in fibroblasts and is barely detectable in CD4 lymphocytes. 相似文献
95.
Chan TL Yuen ST Kong CK Chan YW Chan AS Ng WF Tsui WY Lo MW Tam WY Li VS Leung SY 《Nature genetics》2006,38(10):1178-1183
Epimutations in the germline, such as methylation of the MLH1 gene, may contribute to hereditary cancer syndrome in human, but their transmission to offspring has never been documented. Here we report a family with inheritance, in three successive generations, of germline allele-specific and mosaic hypermethylation of the MSH2 gene, without evidence of DNA mismatch repair gene mutation. Three siblings carrying the germline methylation developed early-onset colorectal or endometrial cancers, all with microsatellite instability and MSH2 protein loss. Clonal bisulfite sequencing and pyrosequencing showed different methylation levels in different somatic tissues, with the highest level recorded in rectal mucosa and colon cancer tissue, and the lowest in blood leukocytes. This mosaic state of germline methylation with different tissue distribution could act as the first hit and provide a mechanism for genetic disease inheritance that may deviate from the mendelian pattern and be overlooked in conventional leukocyte-based genetic diagnosis strategy. 相似文献
96.
Glycogen synthase kinase 3β and Alzheimer’s disease: pathophysiological and therapeutic significance 总被引:3,自引:0,他引:3
Balaraman Y Limaye AR Levey AI Srinivasan S 《Cellular and molecular life sciences : CMLS》2006,63(11):1226-1235
Alzheimer’s disease (AD) is a neurodegenerative disorder associated with cognitive and behavioral dysfunction and is the leading
cause of dementia in the elderly. Several studies have implicated molecular and cellular signaling cascades involving the
serine-threonine kinase, glycogen synthase kinase β(GSK-3β) in the pathogenesis of AD. GSK-3β may play an important role in
the formation of neurofibrillary tangles and senile plaques, the two classical pathological hallmarks of AD. In this review,
we discuss the interaction between GSK-3β and several key molecules involved in AD, including the presenilins, amyloid precursor
protein, tau, and β-amyloid. We identify the signal transduction pathways involved in the pathogenesis of AD, including Wnt,
Notch, and the PI3 kinase/Akt pathway. These may be potential therapeutic targets in AD.
Received 19 December 2005; received after revision 24 January 2006; accepted 6 February 2006 相似文献
97.
CXorf6 is a causative gene for hypospadias 总被引:3,自引:0,他引:3
Fukami M Wada Y Miyabayashi K Nishino I Hasegawa T Nordenskjöld A Camerino G Kretz C Buj-Bello A Laporte J Yamada G Morohashi K Ogata T 《Nature genetics》2006,38(12):1369-1371
46,XY disorders of sex development (DSD) refer to a wide range of abnormal genitalia, including hypospadias, which affects approximately 0.5% of male newborns. We identified three different nonsense mutations of CXorf6 in individuals with hypospadias and found that its mouse homolog was specifically expressed in fetal Sertoli and Leydig cells around the critical period for sex development. These data imply that CXorf6 is a causative gene for hypospadias. 相似文献
98.
99.
Molecular and Cellular Basis of Regeneration and Tissue Repair 总被引:2,自引:0,他引:2
The Xenopus tadpole is a favourable organism for regeneration research because it is suitable for a wide range of micromanipulative procedures and for a wide range of transgenic methods. Combination of these techniques enables genes to be activated or inhibited at specific times and in specific tissue types to a much higher degree than in any other organism capable of regeneration. Regenerating systems include the tail, the limb buds and the lens. The study of tail regeneration has shown that each tissue type supplies the cells for its own replacement: there is no detectable de-differentiation or metaplasia. Signalling systems needed for regeneration include the BMP and Notch signalling pathways, and perhaps also the Wnt and FGF pathways. The limb buds will regenerate completely at early stages, but not once they are fully differentiated. This provides a good opportunity to study the loss of regenerative ability using transgenic methods. 相似文献
100.
The urokinase receptor and integrins in cancer progression 总被引:2,自引:0,他引:2
Enhanced levels of expression of urokinase receptor (uPAR) and certain integrins have been linked to cancer cell progression. This has classically been attributed to matrix degradation via the activation of the urokinase (uPA)/plasmin system and modulation of cell motility and survival through integrin engagement. More recently, uPAR has been shown to play multiple roles independent of protease activity. Specifically, uPAR has been shown to be intimately involved in the regulation of cell adhesion, migration and proliferation in part through interactions with other membrane partners, including integrins. The goal of this review is to summarize recent insights in the function of uPAR/integrin interactions, to provide a framework for understanding the importance of these interactions in the context of cancer, and to highlight its potential as a target for therapeutic intervention. 相似文献