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排序方式: 共有1611条查询结果,搜索用时 15 毫秒
941.
Naoya Hashimoto Akihiro Tsuboi Naoki Kagawa Yasuyoshi Chiba Shuichi Izumoto Manabu Kinoshita Noriyuki Kijima Yoshihiro Oka Soyoko Morimoto Hiroko Nakajima Satoshi Morita Junichi Sakamoto Sumiyuki Nishida Naoki Hosen Yusuke Oji Norio Arita Toshiki Yoshimine Haruo Sugiyama 《Cancer immunology, immunotherapy : CII》2015,64(6):707-716
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945.
Toshiaki Matsui Takashi Kondo Yoshitaka Nishita Satoshi Itadani Hiroshi Tsuruta Setsuko Fujita Nagashige Omawari Masaru Sakai Shuichi Nakazawa Akihito Ogata Hideaki Mori Wataru Kamoshima Kouichiro Terai Hiroyuki Ohno Takaaki Obata Hisao Nakai Masaaki Toda 《Bioorganic & medicinal chemistry》2002,10(12):136-3805
Design and synthesis of metabolically stabilized inhibitors of TNF-alpha production, which could be new drug candidates, are reported. Conformational analysis of an active diastereoisomer was performed based on biological evaluations of the conformationally fixed indane derivatives 17 and 18. Structure-activity relationships (SARs) based on biological evaluations of the optically active derivatives are also discussed. Full details including chemistry are reported. 相似文献
946.
Shuichi Takeda Shiho Minakata Ryotaro Koike Ichiro Kawahata Akihiro Narita Masashi Kitazawa Motonori Ota Tohru Yamakuni Yuichiro Maéda Yasushi Nitanai 《PLoS biology》2010,8(7)
The actin capping protein (CP) tightly binds to the barbed end of actin filaments, thus playing a key role in actin-based lamellipodial dynamics. V-1 and CARMIL proteins directly bind to CP and inhibit the filament capping activity of CP. V-1 completely inhibits CP from interacting with the barbed end, whereas CARMIL proteins act on the barbed end-bound CP and facilitate its dissociation from the filament (called uncapping activity). Previous studies have revealed the striking functional differences between the two regulators. However, the molecular mechanisms describing how these proteins inhibit CP remains poorly understood. Here we present the crystal structures of CP complexed with V-1 and with peptides derived from the CP-binding motif of CARMIL proteins (CARMIL, CD2AP, and CKIP-1). V-1 directly interacts with the primary actin binding surface of CP, the C-terminal region of the α-subunit. Unexpectedly, the structures clearly revealed the conformational flexibility of CP, which can be attributed to a twisting movement between the two domains. CARMIL peptides in an extended conformation interact simultaneously with the two CP domains. In contrast to V-1, the peptides do not directly compete with the barbed end for the binding surface on CP. Biochemical assays revealed that the peptides suppress the interaction between CP and V-1, despite the two inhibitors not competing for the same binding site on CP. Furthermore, a computational analysis using the elastic network model indicates that the interaction of the peptides alters the intrinsic fluctuations of CP. Our results demonstrate that V-1 completely sequesters CP from the barbed end by simple steric hindrance. By contrast, CARMIL proteins allosterically inhibit CP, which appears to be a prerequisite for the uncapping activity. Our data suggest that CARMIL proteins down-regulate CP by affecting its conformational dynamics. This conceptually new mechanism of CP inhibition provides a structural basis for the regulation of the barbed end elongation in cells. 相似文献
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948.
Osanai Yui Flittner Anna Janes Jasmine K. Theobald Phil Pendall Elise Newton Paul C. D. Hovenden Mark J. 《Plant and Soil》2012,350(1-2):365-378
Plant and Soil - Decomposition of organic matter varies depending upon interactions between the composition of the organic matter and the source of the microbial community, with differences in... 相似文献
949.
Kazufumi Ikuta Koichi Hashimoto Hisatoshi Kaneko Shuichi Mori Kazutaka Ohashi Tatsuo Suzutani 《Microbiology and immunology》2012,56(12):805-809
The inhibitory effects of an extract of the blackcurrant (Ribes nigrum L.) against pathogens associated with oral, nasopharyngeal and upper respiratory infectious diseases; namely respiratory syncytial virus (RSV), influenza virus A and B (IFV‐A and IFV‐B), adenovirus (AdV), herpes simplex virus type 1, Haemophilus influenzae type B, Streptococcus pneumoniae and Streptococcus mutans, were investigated. Less than 1% concentration of extract of blackcurrant inhibited replication of RSV, IFV‐A and ‐B and HSV‐1 by over 50% and a 10% extract inhibited adsorption of these viruses onto the cell surface by over 95%. The effects on AdV were much less pronounced; the half minimal inhibitory concentration of AdV replication was 2.54 ± 0.26, and a 10% concentration of the extract inhibited AdV adsorption on the cell surface by 72.9 ± 3.4%. The antibacterial activities of the blackcurrant were evaluated based on its efficacy as a disinfectant. A 10% extract disinfected 99.8% of H. Influenzae type B and 78.9% of S. pneumoniae in 10 min, but had no demonstrable effect against S. mutans. The blackcurrant extract still showed antiviral and antibacterial activities after the pH had been made neutral with sodium hydroxide, suggesting that these activities are not the result of acidic reactions or of components precipitated at a neutral pH. These findings demonstrate the potential of blackcurrant extract as a functional food for oral care. 相似文献
950.
Sasaki S Imaeda T Hayase Y Shimizu Y Kasai S Cho N Harada M Suzuki N Furuya S Fujino M 《Bioorganic & medicinal chemistry letters》2002,12(16):2073-2077
The design and synthesis of a new class of nonpeptide luteinizing hormone-releasing hormone (LHRH) receptor antagonists, the 2-phenylimidazo[1,2-a]pyrimidin-5-ones, is reported. Among compounds described in this study, we identified the potent antagonist 15b with nanomolar in vitro functional antagonism. The result might suggest that the heterocyclic 5-6-ring system possessing a pendant phenyl group attached to the five-membered ring is the important structural feature for a scaffold of small molecule LHRH antagonists. 相似文献