全文获取类型
收费全文 | 485篇 |
免费 | 22篇 |
专业分类
507篇 |
出版年
2024年 | 1篇 |
2022年 | 3篇 |
2021年 | 10篇 |
2020年 | 4篇 |
2019年 | 8篇 |
2018年 | 4篇 |
2017年 | 8篇 |
2016年 | 12篇 |
2015年 | 16篇 |
2014年 | 20篇 |
2013年 | 30篇 |
2012年 | 38篇 |
2011年 | 28篇 |
2010年 | 15篇 |
2009年 | 15篇 |
2008年 | 35篇 |
2007年 | 36篇 |
2006年 | 35篇 |
2005年 | 36篇 |
2004年 | 28篇 |
2003年 | 24篇 |
2002年 | 24篇 |
2001年 | 5篇 |
2000年 | 12篇 |
1999年 | 10篇 |
1998年 | 4篇 |
1997年 | 6篇 |
1996年 | 4篇 |
1995年 | 5篇 |
1994年 | 2篇 |
1993年 | 2篇 |
1992年 | 4篇 |
1991年 | 2篇 |
1990年 | 1篇 |
1989年 | 1篇 |
1988年 | 5篇 |
1982年 | 2篇 |
1981年 | 1篇 |
1980年 | 6篇 |
1979年 | 1篇 |
1978年 | 2篇 |
1977年 | 1篇 |
1974年 | 1篇 |
排序方式: 共有507条查询结果,搜索用时 15 毫秒
71.
Direct interaction of nuclear liver X receptor-beta with ABCA1 modulates cholesterol efflux 总被引:1,自引:0,他引:1
Hozoji M Munehira Y Ikeda Y Makishima M Matsuo M Kioka N Ueda K 《The Journal of biological chemistry》2008,283(44):30057-30063
72.
MDR1 (multidrug resistance 1)/P-glycoprotein is an ATP-driven transporter which excretes a wide variety of structurally unrelated hydrophobic compounds from cells. It is suggested that drugs bind to MDR1 directly from the lipid bilayer and that cholesterol in the bilayer also interacts with MDR1. However, the effects of cholesterol on drug-MDR1 interactions are still unclear. To examine these effects, human MDR1 was expressed in insect cells and purified. The purified MDR1 protein was reconstituted in proteoliposomes containing various concentrations of cholesterol and enzymatic parameters of drug-stimulated ATPase were compared. Cholesterol directly binds to purified MDR1 in a detergent soluble form and the effects of cholesterol on drug-stimulated ATPase activity differ from one drug to another. The effects of cholesterol on K(m) values of drug-stimulated ATPase activity were strongly correlated with the molecular mass of that drug. Cholesterol increases the binding affinity of small drugs (molecular mass <500 Da), but does not affect that of drugs with a molecular mass of between 800 and 900 Da, and suppresses that of valinomycin (molecular mass >1000 Da). V(max) values for rhodamine B and paclitaxel are also increased by cholesterol, suggesting that cholesterol affects turnover as well as drug binding. Paclitaxel-stimulated ATPase activity of MDR1 is enhanced in the presence of stigmasterol, sitosterol and campesterol, as well as cholesterol, but not ergosterol. These results suggest that the drug-binding site of MDR1 may best fit drugs with a molecular mass of between 800 and 900 Da, and that cholesterol may support the recognition of smaller drugs by adjusting the drug-binding site and play an important role in the function of MDR1. 相似文献
73.
Hidetaka Kosako Yukiko Gotoh Eisuke Nishida 《Development, growth & differentiation》1996,38(6):577-582
Mitogen-activated protein kinase (MAPK) was originally identified as a serine/threonine protein kinase that is rapidly activated in response to various growth factors and tumor promoters in mammalian cultured cells. The kinase cascade including MAPK and its direct activator, MAPK kinase (MAPKK), is now believed to transmit various extracellular signals into their intracellular targets in eukaryotic cells. It has been reported that activation of MAPKK and MAPK occurs during the meiotic maturation of oocytes in several species, including Xenopus laevis . Studies with neutralizing antibodies against MAPKK, MAPK phosphatases and constitutively active MAPKK or MAPK have revealed a crucial role of the MAPKK/MAPK cascade in a number of developmental processes in Xenopus oocytes and embryos. 相似文献
74.
75.
Seno T Hamaguchi M Ashihara E Kohno M Ishino H Yamamoto A Kadoya M Nakamura K Murakami K Matoba S Maekawa T Kawahito Y 《PloS one》2011,6(10):e25541
Aim
15-Deoxy-Δ12,14 Prostaglandin J2 (15d-PGJ2) is a ligand of peroxisome proliferator-activated receptor γ (PPARγ) having diverse effects such as the differentiation of adipocytes and atherosclerotic lesion formation. 15d-PGJ2 can also regulate the expression of inflammatory mediators on immune cells independent of PPARγ. We investigated the antiatherogenic effect of 15d-PGJ2.Methods
We fed apolipoprotein (apo) E-deficient female mice a Western-type diet from 8 to 16 wk of age and administered 1 mg/kg/day 15d-PGJ2 intraperitoneally. We measured atherosclerotic lesions at the aortic root, and examined the expression of macrophage and inflammatory atherosclerotic molecules by immunohistochemical and real-time PCR in the lesion.Results
Atherosclerotic lesion formation was reduced in apo E-null mice treated with 15d-PGJ2, as compared to in the controls. Immunohistochemical and real-time PCR analyses showed that the expression of MCP-1, TNF-α, and MMP-9 in atherosclerotic lesions was significantly decreased in 15d-PGJ2 treated mice. The 15d-PGJ2 also reduced the expression of macrophages and RelA mRNA in atherosclerotic lesions.Conclusion
This is the first report 15d-PGJ2, a natural PPARγ agonist, can improve atherosclerotic lesions in vivo. 15d-PGJ2 may be a beneficial therapeutic agent for atherosclerosis. 相似文献76.
Castellanos-Martinez S Gómez MC Hochberg FG Gestal C Furuya H 《The Journal of parasitology》2011,97(2):265-269
A new species of dicyemid mesozoan is described from Octopus hubbsorum Berry, 1953, collected in the south of Bahia de La Paz, Baja California Sur, México. Dicyema guaycurense n. sp. is a medium-size species that reaches about 1,600 μm in length. It occurs in folds of the renal appendages. The vermiform stages are characterized as having 22 peripheral cells, a conical calotte, and an axial cell that extends to the base of the propolar cells. Infusoriform embryos consist of 39 cells; 1 nucleus is present in each urn cell and the refringent bodies are solid. This is the first of a dicyemid species from a host collected in the Gulf of California. 相似文献
77.
PKA contributes to many physiological processes, including glucose homeostasis and cell migration. The substrate specificity of PKA is low compared with other kinases; thus, complex formation with A-kinase-anchoring proteins is important for the localization of PKA in specific subcellular regions and the phosphorylation of specific substrates. Here, we show that PKA forms a complex with WAVE2 (Wiskott-Aldrich syndrome protein family verprolin-homologous protein 2) in MDA-MB-231 breast cancer cells and mouse brain extracts. Two separate regions of WAVE2 are involved in WAVE2-PKA complex formation. This complex localizes to the leading edge of MDA-MB-231 cells. PKA activation results in enlargement of the membrane protrusion. WAVE2 depletion impairs PKA localization at membrane protrusions and the enlargement of membrane protrusion induced by PKA activation. Together, these results suggest that WAVE2 works as an A-kinase-anchoring protein that recruits PKA at membrane protrusions and plays a role in the enlargement of membrane protrusions induced by PKA activation. 相似文献
78.
Enoki N Kiyoshima T Sakai T Kobayashi I Takahashi K Terada Y Sakai H 《Journal of molecular histology》2007,38(4):321-332
This study investigated the age-dependent changes in the number of BrdU- and TUNEL-positive cells in murine gingival tissue
and submandibular gland, and compared the findings with those in other tissues and organs. The cell proliferative activity
was decreased after 20 weeks of age in epithelial cells of the gingiva, tongue, buccal mucosa and skin. A decreased cell proliferative
activity was also associated with aging in the liver and kidney parenchymal cells. Meanwhile, cell death showed peculiar changes
in gingival subepithelial tissue, and mucous and serous acini of the submandibular gland. An increase of TUNEL-positive cells
was demonstrated in gingival subepithelial tissue after 20-week-old of age. A significant increase of TUNEL-positive cells
was also found in the mucous acinar cells in the 20-week-old mice and in the serous acini after 20 weeks. The fluctuation
in the number of TUNEL-positive cells in the subepithelial tissue of the skin, and BrdU- and TUNEL-positive staining ratios
in the liver was smaller than that in other tissue and organs throughout life. This study may provide useful information for
better understanding the influence of aging on the functional alteration that occurs in the gingival tissue and submandibular
gland of the elderly. 相似文献
79.
Murata H Futami J Kitazoe M Yonehara T Nakanishi H Kosaka M Tada H Sakaguchi M Yagi Y Seno M Huh NH Yamada H 《Journal of biochemistry》2008,144(4):447-455
The glutathione S-transferase (GST)-fused protein expression system has been extensively used to generate a large quantity of proteins and has served for functional analysis in vitro. In this study, we developed a novel approach for the efficient intracellular delivery of GST-fused proteins into living cells to expand their usefulness up to in vivo use. Since protein cationization techniques are powerful strategies for efficient intracellular uptake by adsorptive-mediated endocytosis, GST-fused proteins were cationized by forming a complex with a polycationic polyethylenimine (PEI)-glutathione conjugate. On screening of protein transduction, optimized PEI-glutathione conjugate for protein transduction was characterized by a partly oligomerized mixture of PEI with average molecular masses of 600 (PEI600) modified with multiple glutathiones, which could have sufficient avidity for GST. Furthermore, enhanced endosomal escape of transduced GST-fused proteins was observed when they were delivered with a glutathione-conjugated PEI600 derivative possessing a hydroxybutenyl moiety. These results were confirmed by both intracellular confocal imaging of GST-fused green fluorescent protein and activation of an endogenous growth signal transduction pathway by a GST-fused constitutively active mutant of a kinase protein. These PEI-glutathione conjugates seem to be convenient molecular tools for protein transduction of widely used GST-fused proteins. 相似文献
80.
Tomomi Shida-Sakazume Yosuke Endo-Sakamoto Motoharu Unozawa Chonji Fukumoto Ken Shimada Atsushi Kasamatsu Katsunori Ogawara Hidetaka Yokoe Masashi Shiiba Hideki Tanzawa Katsuhiro Uzawa 《PloS one》2015,10(3)