全文获取类型
收费全文 | 3196篇 |
免费 | 220篇 |
国内免费 | 1篇 |
出版年
2023年 | 11篇 |
2022年 | 23篇 |
2021年 | 53篇 |
2020年 | 35篇 |
2019年 | 47篇 |
2018年 | 71篇 |
2017年 | 54篇 |
2016年 | 98篇 |
2015年 | 173篇 |
2014年 | 178篇 |
2013年 | 205篇 |
2012年 | 277篇 |
2011年 | 243篇 |
2010年 | 151篇 |
2009年 | 145篇 |
2008年 | 203篇 |
2007年 | 190篇 |
2006年 | 152篇 |
2005年 | 147篇 |
2004年 | 157篇 |
2003年 | 146篇 |
2002年 | 86篇 |
2001年 | 70篇 |
2000年 | 74篇 |
1999年 | 59篇 |
1998年 | 16篇 |
1997年 | 21篇 |
1996年 | 24篇 |
1995年 | 15篇 |
1994年 | 9篇 |
1993年 | 12篇 |
1992年 | 23篇 |
1991年 | 16篇 |
1990年 | 15篇 |
1989年 | 13篇 |
1988年 | 15篇 |
1987年 | 16篇 |
1986年 | 16篇 |
1985年 | 13篇 |
1984年 | 13篇 |
1983年 | 13篇 |
1982年 | 10篇 |
1981年 | 10篇 |
1980年 | 10篇 |
1979年 | 8篇 |
1978年 | 6篇 |
1975年 | 11篇 |
1974年 | 8篇 |
1972年 | 6篇 |
1971年 | 6篇 |
排序方式: 共有3417条查询结果,搜索用时 31 毫秒
111.
112.
Jong Taik Moon Sung Hoon Ha So Hyung Lee Tae Hui Kwon Chun Rim Oh Young Deuk Kim Jungahn Kim Dong Joon Choo Jae Yeol Lee 《Bioorganic & medicinal chemistry letters》2010,20(1):52-55
First total synthesis of methylgerambullone (MGB, 1) isolated from Glycosmis angustifolia was completed via a convergent route. The effect of MGB on the contractile responses of the isolated guinea-pig ileum induced by acetylcholine was investigated. As a result, it showed a potent relaxation rate (78.66 ± 4.30% at 100 mg/L) in a concentration-dependent manner on longitudinal smooth muscle contraction of isolated guinea-pig ileum induced by 1 μM acetylcholine. 相似文献
113.
Both platelet-derived growth factor receptor (PDGFR)-alpha and PDGFR-beta promote murine fibroblast cell migration 总被引:3,自引:0,他引:3
Cell motility plays a critical role for many physiological and pathological processes including wound healing, fibrosis, angiogenesis, and tumor metastasis. Platelet-derived growth factor (PDGF) is among the most potent stimuli for mesenchymal cell migration. The PDGF B-chain homodimer PDGF BB activates both alpha- and beta-receptor subunits (alpha-PDGFR and beta-PDGFR), and promotes cell migration in many cell types including fibroblasts and smooth muscle cells. PDGF-A chain homodimer PDGF AA activates alpha-PDGFR only, and its role for cell migration is still debatable. PDGF BB, but not PDGF AA, induces smooth muscle cell migration. Interestingly, alpha-PDGFR was shown to antagonize beta-PDGFR-induced smooth muscle cell migration. In the present study, we investigated the role of alpha-PDGFR and beta-PDGFR in PDGF-mediated cell migration of murine fibroblasts (NIH 3T3). Unlike smooth muscle cells, both PDGF AA and PDGF BB promoted NIH 3T3 cell migration. The effect of PDGF BB activation of beta-PDGFR alone for cell migration was examined using previously established NIH 3T3 clones in which alpha-PDGFR signaling is inhibited by a dominant-negative alpha-PDGFR, or an antisense construct of alpha-PDGFR. PDGF BB activation of beta-PDGFR alone was sufficient to induce cell migration, but the efficiency was significantly lower compared to PDGF activation of both receptors. These results showed that both alpha- and beta-PDGFRs promote fibroblast cell migration and their effects are additive. Taken together, we propose that cell-type specific alpha-PDGFR signaling is critical for regulation of mesenchymal cell migration in response to PDGF isoform, whereas beta-PDGFR mainly promotes cell migration. 相似文献
114.
115.
A cysteine-rich adipose tissue-specific secretory factor inhibits adipocyte differentiation 总被引:94,自引:0,他引:94
A 12.5-kDa cysteine-rich adipose tissue-specific secretory factor (ADSF/resistin) is a novel secreted protein rich in serine and cysteine residues with a unique cysteine repeat motif of CX(12)CX(8)CXCX(3)CX(10)CXCXCX(9)CC. A single 0.8-kilobase mRNA coding for this protein was found in various murine white adipose tissues including inguinal and epididymal fats and also in brown adipose tissue but not in any other tissues examined. Two species of mRNAs with sizes of 1.4 and 0.8 kilobases were found in rat adipose tissue. Sequence analysis indicates that this is because of two polyadenylation signals, the proximal one with the sequence AATACA with a single base mismatch from murine AATAAA and the distal consensus sequence AATAAA. The mRNA level was markedly increased during 3T3-L1 and primary preadipocyte differentiation into adipocytes. Its expression in adipose tissue is under tight nutritional and hormonal regulation; the mRNA level was very low during fasting and increased 25-fold when fasted mice were refed a high carbohydrate diet. It was also very low in adipose tissue of streptozotocin-diabetes and increased 23-fold upon insulin administration. Upon treatment with the conditioned medium from COS cells transfected with the expression vector, conversion of 3T3-L1 cells to adipocytes was inhibited by 80%. The regulated expression pattern suggesting this factor as an adipose sensor for the nutritional state of the animals and the inhibitory effect on adipocyte differentiation implicate its function as a feedback regulator of adipogenesis. 相似文献
116.
117.
Yun TJ Tallquist MD Aicher A Rafferty KL Marshall AJ Moon JJ Ewings ME Mohaupt M Herring SW Clark EA 《Journal of immunology (Baltimore, Md. : 1950)》2001,166(3):1482-1491
Osteoprotegerin (OPG) is a CD40-regulated gene in B cells and dendritic cells (DCs). We investigated the role of OPG in the immune system by generating opg(-/-) mice. Like its role as a regulator of bone metabolism, OPG also influences processes in the immune system, notably in B cell development. Ex vivo, opg(-/-) pro-B cells have enhanced proliferation to IL-7, and in opg(-/-) spleen, there is an accumulation of type 1 transitional B cells. Furthermore, opg(-/-) bone marrow-derived DCs are more effective in stimulating allogeneic T cells than control DCs. When challenged with a T-dependent Ag, opg(-/-) mice had a compromised ability to sustain an IgG3 Ag-specific response. Thus, in the immune system, OPG regulates B cell maturation and development of efficient Ab responses. 相似文献
118.
Humphreys MJ Moon RP Klinder A Fowler SD Rupp K Bur D Ridley RG Berry C 《FEBS letters》1999,463(1-2):43-48
The gene encoding an aspartic proteinase precursor (proplasmepsin) from the rodent malaria parasite Plasmodium berghei has been cloned. Recombinant P. berghei plasmepsin hydrolysed a synthetic peptide substrate and this cleavage was prevented by the general aspartic proteinase inhibitor, isovaleryl pepstatin and by Ro40-4388, a lead compound for the inhibition of plasmepsins from the human malaria parasite Plasmodium falciparum. Southern blotting detected only one proplasmepsin gene in P. berghei. Two plasmepsins have previously been reported in P. falciparum. Here, we describe two further proplasmepsin genes from this species. The suitability of P. berghei as a model for the in vivo evaluation of plasmepsin inhibitors is discussed. 相似文献
119.
H K Song J Y Lee M G Lee J Moon K Min J K Yang S W Suh 《Journal of molecular biology》1999,293(4):753-761
"Two-component" phosphorelay signal transduction systems constitute a potential target for antibacterial and antifungal agents, since they are found exclusively in prokaryotes and lower eukaryotes (yeast, fungi, slime mold, and plants) but not in mammalian organisms. Saccharomyces cerevisiae Ypd1p, a key intermediate in the osmosensing multistep phosphorelay signal transduction, catalyzes the phosphoryl group transfer between response regulators. Its 1.8 A structure, representing the first example of a eukaryotic phosphorelay protein, contains a four-helix bundle as in the HPt domain of Escherichia coli ArcB sensor kinase. However, Ypd1p has a 44-residue insertion between the last two helices of the helix bundle. The side-chain of His64, the site of phosphorylation, protrudes into the solvent. The structural resemblance between Ypd1p and ArcB HPt domain suggests that both prokaryotes and lower eukaryotes utilize the same basic protein fold for phosphorelay signal transduction. This study sheds light on the best characterized eukaryotic phosphorelay system. 相似文献
120.
Kim IS Kim ER Nam HJ Chin MO Moon YH Oh MR Yeo UC Song SM Kim JS Uhm MR Beck NS Jin DK 《Hormone research》1999,52(5):235-240
McCune-Albright syndrome (MAS) is a sporadic disease characterized by café-au-lait spots, polyostotic fibrous dysplasia and hyperfunctional endocrinopathies. To elucidate the mechanism of skin pigmentation, melanocytes, keratinocytes and fibroblasts were primary cultured from the café-au-lait spot of a MAS patient. Then, mutational analysis and morphologic evaluation were performed. Also, cAMP level and tyrosinase gene expression in cultured cells were determined. Only Gsalpha mutation was found in affected melanocytes and the cAMP level in affected melanocytes was higher than that of normal melanocytes. The mRNA expression of tyrosinase gene was increased in the affected melanocytes. This study suggests that skin pigmentation of MAS results from activating mutation of Gsalpha in melanocytes and the mechanism involves the c-AMP-mediated tyrosinase gene activation. 相似文献