全文获取类型
收费全文 | 238篇 |
免费 | 8篇 |
出版年
2023年 | 1篇 |
2022年 | 1篇 |
2019年 | 2篇 |
2018年 | 1篇 |
2017年 | 4篇 |
2016年 | 3篇 |
2015年 | 8篇 |
2014年 | 6篇 |
2013年 | 10篇 |
2012年 | 21篇 |
2011年 | 24篇 |
2010年 | 12篇 |
2009年 | 8篇 |
2008年 | 15篇 |
2007年 | 15篇 |
2006年 | 13篇 |
2005年 | 10篇 |
2004年 | 20篇 |
2003年 | 12篇 |
2002年 | 20篇 |
2001年 | 1篇 |
2000年 | 3篇 |
1999年 | 3篇 |
1998年 | 1篇 |
1997年 | 3篇 |
1996年 | 5篇 |
1995年 | 5篇 |
1994年 | 2篇 |
1993年 | 2篇 |
1992年 | 1篇 |
1990年 | 3篇 |
1989年 | 1篇 |
1986年 | 1篇 |
1985年 | 1篇 |
1984年 | 3篇 |
1982年 | 3篇 |
1980年 | 1篇 |
1978年 | 1篇 |
排序方式: 共有246条查询结果,搜索用时 15 毫秒
101.
Morita M Takahashi I Kanai M Okafuji F Iwashima M Hayashi T Watanabe S Hamazaki T Shimozawa N Suzuki Y Furuya H Yamada T Imanaka T 《FEBS letters》2005,579(2):409-414
The purpose of the present study is to identify bioactive compounds with potential for X-linked adrenoleukodystrophy (X-ALD) pharmacological therapy. Various plant natural products including flavonoids were tested for their ability to ameliorate the abnormality of very long chain fatty acid (VLCFA) metabolism in cultured skin-fibroblasts from X-ALD patients. Of the compounds tested, baicalein 5,6,7-trimethyl ether (baicalein-tri-Me) was found to significantly stimulate the VLCFA beta-oxidation activity. Furthermore, the incorporation of [1-(14)C]lignoceric acid into cholesteryl esters was markedly reduced towards the normal level and the VLCFA (C24:0 and C26:0) content was decreased. These results make baicalein-tri-Me a candidate for the therapeutic compound for X-ALD. 相似文献
102.
Conditional activation of RhoA suppresses the epithelial to mesenchymal transition at the primitive streak during mouse gastrulation 总被引:3,自引:0,他引:3
Fuse T Kanai Y Kanai-Azuma M Suzuki M Nakamura K Mori H Hayashi Y Mishina M 《Biochemical and biophysical research communications》2004,318(3):665-672
Gastrulation is a pivotal event of mouse early embryogenesis. In telencephalin (TLCN)-Cre mice carrying the Cre recombinase gene inserted into the translational initiation site of the TLCN gene, Cre-mediated recombination took place at the postimplantation stage. To examine the role of RhoA signaling in early embryogenesis, we produced Rho36 mice carrying constitutively active RhoA(G14V) gene inducible by Cre recombinase and crossed with TLCN-Cre mice. In doubly transgenic embryos at the gastrulation stage, there appeared an abnormal bulge of cells protruded from the primitive streak region into the amniotic cavity. The bulged cell mass expressed the epiblast marker gene Oct3 and E-cadherin, but not the primitive streak marker gene T except for the basal portion. These results suggest that the conditional activation of RhoA signaling suppressed the epithelial to mesenchymal transition at the primitive streak during mouse gastrulation. 相似文献
103.
Nonylphenol induces the death of neural stem cells due to activation of the caspase cascade and regulation of the cell cycle 总被引:6,自引:0,他引:6
Kudo C Wada K Masuda T Yonemura T Shibuya A Fujimoto Y Nakajima A Niwa H Kamisaki Y 《Journal of neurochemistry》2004,88(6):1416-1423
Endocrine disruptors (EDs) are a great concern throughout the world, because they have adverse effects on human health and wildlife. In the present study, we investigated the effects of EDs on the proliferation and survival of murine neural stem cells (NSCs). In contrast to bisphenol A, phthalic acid benzyl n-butyl ester, phthalic acid di-n-butyl ester and phthalic acid di(2-ethylhexyl) ester, the treatment of NSCs with 4-nonylphenol for 24 h inhibited cell growth in a concentration-dependent manner. In addition, treatment with 4-nonylphenol resulted in nuclear condensation and DNA fragmentation (morphological changes due to apoptosis) in NSCs after 12 h of exposure, and activated caspase-3 after 6 h and 9 h of exposure. Furthermore, an exposure to 4-nonylphenol led to the accumulation of cells at the G2/M phase interface and down-regulated the protein levels of cyclin A and B1, which are the major regulatory proteins at the G2 to M transition of the cell cycle. Together, these results indicate that, in contrast to other EDs, 4-nonylphenol may exhibit a potent cytotoxicity through apoptosis via the caspase cascade and cell cycle arrest at the G2/M phase, and suggest that 4-nonylphenol may affect neurogenesis in the CNS. 相似文献
104.
Osteopontin (OPN) is a highly acidic secreted phosphoprotein that binds to cells via an RGD (arginine-glycine-aspartic acid) cell adhesion sequence that recognizes the alphaVbeta3 integrin. OPN may regulate the formation and remodeling of bone. To elucidate the function of OPN in bone tissue, we examined the overexpression of OPN in osteoblasts in vitro and in vivo using an adenoviral vector carrying an OPN cDNA (Adv-OPN). Rat bone marrow-derived osteoblasts infected with Adv-OPN were examined by Western blotting, immunofluorescence, nodule formation measurements, assay of alkaline phosphatase (ALP) activity, and Northern blotting. The results suggested that not only osteoblast differentiation markers such as osteocalcin and ALP, but nodule formation and ALP activity are markedly enhanced by OPN overexpression in the case of viral infection. On the contrary, when Adv-OPN and uninfected osteoblasts were implanted into subcutaneous sites with a porous ceramic scaffold, the ALP activity and calcium content of the OPN-infected composite were higher than in uninfected composites, however, the differences were smaller than expected from the in vitro experiments. We speculate that the difference in the result of in vitro and in vivo experiments originates from the inhibitory effect of secreted OPN on the crystal growth of apatite in vivo, which competes with the induced activity of osteoblasts. 相似文献
105.
Ito C Itoigawa M Onoda S Hosokawa A Ruangrungsi N Okuda T Tokuda H Nishino H Furukawa H 《Phytochemistry》2005,66(5):567-572
Isolation and structure elucidation of three coumarins, murrayacoumarins A, B, and C, together with eight known coumarins, from the leaves of Murraya siamensis Craib collected in Thailand are described. Results of a primary screening of inhibitory effects of seven of these compounds on 12-O-tetradecanoylphorbol-13-acetate-induced Epstein-Barr virus early antigen activation in Raji cells are also presented. 相似文献
106.
Mineo Shimizu Toshimi Ito Satoshi Terashima Toshimitsu Hayashi Munehisa Arisawa Naokata Morita Shigeki Kurokawa Kiyoshi Ito Yoshinobu Hashimoto 《Phytochemistry》1984,23(9):1885-1888
The inhibitory activities of 73 flavonoids against rat aldose reductase were systematically investigated and cosmosiin, luteolin-7-glucuronide, lonicerin, 6-hydroxyluteolin, kaempferol-3-rhamnoside and avicularin were newly found to be highly active. The degree of inhibition appears to depend on the solvent system used. In general flavones are more active than flavonols and flavanones, glycosides are more active than aglycones, and the number of sugars present affects the activity. 相似文献
107.
Endogenous synthesis of N-methylnorsalsolinol in rat brain during in vivo microdialysis with epinine
Mitsuharu Kajita Toshimitsu Niwa Wakako Maruyama Daiichiro Nakahara Naohito Takeda Hideo Yoshizumi Akira Tatematsu Kazuyoshi Watanabe Makoto Naoi Toshiharu Nagatsu 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》1994,654(2)
The in vivo metabolic pathway for the synthesis of N-methylnorsalsolinol, an analogue of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), was studied in the rat brain. N-Methyldopamine (epinine) was perfused at the striatum of the rat brain by in vivo microdialysis. N-Methylnorsalsolinol (NMNSAL) was identified in the brain dialysate after epinine perfusion using gas chromatography—selected-ion monitoring mass spectrometry (GC—SIM-MS). We demonstrated that NMNSAL could be synthesized from epinine with an aldehyde by the Piclet—Spengler condensation reaction in the rat brain. 相似文献
108.
Jung-Bum Lee Yuko Ohta Kyoko Hayashi Toshimitsu Hayashi 《Carbohydrate research》2010,345(10):1452-1454
A pyruvylated sulfated galactan from Codium fragile is a highly ramified polysaccharide consisting of 3-linked, 3,6-linked, and non-reducing terminal d-galactose with pyruvate and sulfate groups; the glycan exerts anti-herpes simplex virus type 2 effects in vitro and in vivo. This particular polysaccharide was found to stimulate the production of nitric oxide by inducing iNOS at the mRNA and protein levels. In addition, the polysaccharide also induced several cytokine mRNA expressions such as IL-1β, IL-6, IL-10 and TNF-α. Therefore, it appears that the sulfated galactan might possess the immunostimulating effects via activation of macrophages. 相似文献
109.
110.
Hatabu T Hagiwara M Taguchi N Kiyozawa M Suzuki M Kano S Sato K 《Experimental parasitology》2006,112(3):179-183
The in vitro antimalarial activity of the fungal metabolite gliotoxin (GTX) was evaluated, and its mechanism of action was studied. GTX showed plasmodicidal activity against both Plasmodium falciparum chloroquine-resistant strain K-1 and chloroquine-susceptible strain FCR-3. GTX cytotoxicity was significantly lower against a normal liver cell line (Chang Liver cells). The intracellular reduced glutathione level of parasitized and of normal red blood cells was not affected by GTX treatment. However, GTX decreased the chymotrypsin-like activity of parasite proteasomes in a time-dependent manner. The results of this study indicate that GTX possesses plasmodicidal activity and that this effect is due to inhibition of parasite proteasome activity, suggesting that GTX may constitute a useful antimalarial therapy. 相似文献