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排序方式: 共有135条查询结果,搜索用时 15 毫秒
111.
Ken-ichi Kawasaki Miyako Masubuchi Tadakatsu Hayase Susumu Komiyama Fumio Watanabe Hiroshi Fukuda Takeshi Murata Yasuaki Matsubara Kouhei Koyama Hidetoshi Shindoh Hiroshi Sakamoto Kohichi Okamato Atsunori Ohta Asao Katsume Masahiro Aoki Yuko Aoki Nobuo Shimma Masayuki Sudoh Takuo Tsukuda 《Bioorganic & medicinal chemistry letters》2013,23(1):336-339
Hepatitis C virus (HCV) infection represents a serious health-care problem. Previously we reported the identification of NA255 from our natural products library using a HCV sub-genomic replicon cell culture system. Herein, we report how the absolute stereochemistry of NA255 was determined and an enantioselective synthetic method for NA255 derivatives was developed. The structure–activity relationship of the NA255 derivatives and rat pharmacokinetic profiles of the representative compounds are disclosed. 相似文献
112.
H Nagasawa F Nagura S B Mohamad Y Uto J W Zhu T Tsukuda T Hashimoto Y Asakawa H Hori 《Phytomedicine》2000,6(6):403-409
We examined the induction of apoptosis by cytochalasin (cc) derivatives (1-14) isolated from the Japanese fungus Daldinia vernicosa to HCT116 human colon cancer cell line based on their cytotoxicity, DNA ladder and DNA fragmentation ratio in agarose gel electrophoresis, and morphological changes. Most cc derivatives tested here induced apoptosis. Particularly cytochalasin 1 (cc1), monoacetate of 1 (cc1Ac), and cc14 were the most potent apoptosis inducers. These apoptotic activities were stronger than that of cytochalasin D as a known apoptosis inducer in HCT116 cell. However, cc4 and cc12 induced necrosis. The structure-activity relationship including their cytotoxicity will be discussed. 相似文献
113.
114.
115.
S Toki E Tsukuda M Nozawa H Nonaka M Yoshida Y Matsuda 《The Journal of biological chemistry》1992,267(21):14884-14892
ES-242-1 approximately 5 are novel microbial bioxanthracenes which do not contain nitrogen. The ES-242s inhibited the binding of [3H]TCP and [3H]CGS19755 to the N-methyl-D-aspartate (NMDA) receptor complex. They had no effect on the binding of the specific ligands for the non-NMDA receptor. The biochemical and pharmacological properties of ES-242-1 were fully examined since it is the most potent of the five compounds. ES-242-1 is highly specific for the NMDA receptor; it has no effect on other receptors. Kinetic analyses indicated that ES-242-1 inhibited the binding of [3H]TCP and [3H]CGS19755 in a competitive manner, respectively, suggesting that ES-242-1 interacts with both the transmitter recognition site and the channel domain. ES-242-1 selectively inhibited NMDA-induced Ca2+ influx in primary cultures of mouse hippocampal neurons. ES-242-1 also specifically blocked the increase in cyclic GMP accumulation induced by NMDA or L-glutamate in rat cerebellar slices. In a concentration range of 0.1-1.0 microM, ES-242-1 was as potent as MK-801 in preventing glutamate-induced neurotoxicity in primary cultures of mouse hippocampal neurons. These results show that ES-242-1 is a potent and specific antagonist for the NMDA receptor. The antagonistic properties of the ES-242s appear to be due to a novel mechanism of action at the NMDA receptor. 相似文献
116.
Wortmannin, a microbial product inhibitor of myosin light chain kinase. 总被引:18,自引:0,他引:18
S Nakanishi S Kakita I Takahashi K Kawahara E Tsukuda T Sano K Yamada M Yoshida H Kase Y Matsuda 《The Journal of biological chemistry》1992,267(4):2157-2163
We have found that a fungal strain, Talaromyces wortmannin KY12420, produces a potent inhibitor of smooth muscle myosin light chain kinase (MLCK). This active product, designated as MS-54, was isolated and purified from the culture broth of the fungus and identified as wortmannin. The inhibition of MLCK by wortmannin was prevented by a high concentration of ATP. The activity of the catalytic domain, which was disclosed by partial tryptic digestion, was also inhibited by wortmannin. These results suggest that wortmannin acts at or near to the catalytic site of the enzyme. It was shown clearly by kinetic analyses, preincubation studies, and dialysis experiments that the inhibitory action of wortmannin on MLCK was irreversible. Under the condition of preincubation for 3 min, 0.3 microM wortmannin inhibited the activity of MLCK, while 10 microM wortmannin had no effect on the activities of cAMP-dependent protein kinase, cGMP-dependent protein kinase, and calmodulin-dependent protein kinase II, and had little effect on protein kinase C activity. These data expressed clearly the marked selectivity of the compound for MLCK. Furthermore, wortmannin also inhibited both the phosphorylation of myosin light chain and the contraction in rat thoracic aorta stimulated with KCl, which indicates the effectiveness of the compound in the cellular level as an MLCK inhibitor. 相似文献
117.
Motonori Sairenji Shunsuke Yanoma Hisahiko Motohashi Osamu Kobayashi Kenzou Okada Takashi Okamoto Mamoru Tsukuda Makoto Umeda 《Biotherapy》1993,6(4):283-290
We established a cell line (STKM-1) from tumor cells obtained from carcinomatous pleural effusion of a gastric cancer patient. The lymphocytes separated from her peripheral blood or pleural effusion were cryopreserved and immunological experiments were performed after the establishment of the cell line. They were treated with IL-2 or with both IL-2 and mitomycin C (MMC)-treated autologous STKM-1 cells. The cytolytic activity against STKM-1 cells was elevated in lymphocytes cultured with IL-2, and was more prominently augmented in lymphocytes cultured with both IL-2 and MMC-treated STKM-1 cells. The elevation in cytolytic activity was more marked with pleural effusion lymphocytes than with the peripheral blood lymphocytes. The results suggest that the lymphocytes obtained from the pleural effusion would be an excellent source for adoptive immunotherapy.Abbreviations IL-2
interleukin-2
- LAK
lymphokine activated killer
- MLTC
mixed lymphocyte tumor cell culture
- MMC
mitomycin C
- MoAbs
monoclonal antibodies
- TIL
tumor infiltrating lymphocytes 相似文献
118.
Omar Muhamad Ritsuko Tsukuda Yoko Oki Kenji Fujisaki Fusao Nakasuji 《Population Ecology》1994,36(1):53-62
The larvae ofPlutella xylostella were fed on five wild crucifers,Capsella bursa-pastoris, Lepidium virginicum, Cardamine flexuosa, Rorippa indica, R. islandica and a crop, cabbage. The developmental period of the immature stages, adult longevity, preoviposition period, fecundity and morphometrical characters of the adults were measured. The flight activity of the adults was also measured by the tethered flight method. All the wild plants except forR. islandica were less suitable host plants than cabbage, and larvae which were fed on these less suitable plants emerged as smaller adults with shorter wings. The smaller female adults had lower fecundity but a higher flight activity. Smaller adults measured in terms of their pupal weight among individuals fed on the same host plant had longer wings. These smaller adults with longer wing flew more actively. 相似文献
119.
Matsuzaki K Okada T Tsukuda M Ikeda K Sohma Y Chiyomori Y Taniguchi A Nakamura S Ito N Hayashi Y Kiso Y 《Biochemical and biophysical research communications》2008,371(4):777-780
The aggregation of amyloid β-peptide (Aβ) into β-sheet-rich aggregates is a crucial step in the etiology of Alzheimer’s disease. Helical forms of Aβ have been suggested to be intermediates in the aggregation process of the peptide in aqueous phase, micelles and membranes. A stable helical Aβ analog would be useful to investigate the role of helical intermediates in fibrillization by Aβ. Here we designed a helical analog by simply cross-linking the Cys residues of A30C, G37C-Aβ1-42 with 1,6-bismaleimidohexane. The analog assumed a weak α-helical conformation in model membranes mimicking lipid raft microdomains of neuronal membranes under conditions in which the wild-type Aβ1-42 formed a β-sheet, indicating the cross-linking locally induced a helical conformation. Furthermore, addition of equimolar helical Aβ analog significantly reduced the amyloid formation and cytotoxicity by Aβ1-42. Thus, our helical Aβ1-42 is not only a model peptide to investigate the role of helical intermediates in fibrillization by Aβ, but also an inhibitor of Aβ-induced cytotoxicity. 相似文献
120.
Arsenic trioxide augments Chk2/p53-mediated apoptosis by inhibiting oncogenic Wip1 phosphatase 总被引:2,自引:0,他引:2
Yoda A Toyoshima K Watanabe Y Onishi N Hazaka Y Tsukuda Y Tsukada J Kondo T Tanaka Y Minami Y 《The Journal of biological chemistry》2008,283(27):18969-18979
The oncogenic Wip1 phosphatase (PPM1D) is induced upon DNA damage in a p53-dependent manner and is required for inactivation or suppression of DNA damage-induced cell cycle checkpoint arrest and of apoptosis by dephosphorylating and inactivating phosphorylated Chk2, Chk1, and ATM kinases. It has been reported that arsenic trioxide (ATO), a potent cancer chemotherapeutic agent, in particular for acute promyelocytic leukemia, activates the Chk2/p53 pathway, leading to apoptosis. ATO is also known to activate the p38 MAPK/p53 pathway. Here we show that phosphatase activities of purified Wip1 toward phosphorylated Chk2 and p38 in vitro are inhibited by ATO in a dose-dependent manner. Furthermore, DNA damage-induced phosphorylation of Chk2 and p38 in cultured cells is suppressed by ectopic expression of Wip1, and this Wip1-mediated suppression can be restored by the presence of ATO. We also show that treatment of acute promyelocytic leukemia cells with ATO resulted in induction of phosphorylation and activation of Chk2 and p38 MAPK, which are required for ATO-induced apoptosis. Importantly, this ATO-induced activation of Chk2/p53 and p38 MAPK/p53 apoptotic pathways can be enhanced by siRNA-mediated suppression of Wip1 expression, further indicating that ATO inhibits Wip1 phosphatase in vivo. These results exemplify that Wip1 is a direct molecular target of ATO. 相似文献