全文获取类型
收费全文 | 3854篇 |
免费 | 225篇 |
出版年
2023年 | 7篇 |
2022年 | 18篇 |
2021年 | 40篇 |
2020年 | 25篇 |
2019年 | 42篇 |
2018年 | 55篇 |
2017年 | 64篇 |
2016年 | 89篇 |
2015年 | 123篇 |
2014年 | 166篇 |
2013年 | 204篇 |
2012年 | 240篇 |
2011年 | 254篇 |
2010年 | 171篇 |
2009年 | 168篇 |
2008年 | 292篇 |
2007年 | 237篇 |
2006年 | 246篇 |
2005年 | 253篇 |
2004年 | 251篇 |
2003年 | 198篇 |
2002年 | 209篇 |
2001年 | 70篇 |
2000年 | 71篇 |
1999年 | 58篇 |
1998年 | 52篇 |
1997年 | 43篇 |
1996年 | 31篇 |
1995年 | 20篇 |
1994年 | 23篇 |
1993年 | 23篇 |
1992年 | 38篇 |
1991年 | 32篇 |
1990年 | 23篇 |
1989年 | 18篇 |
1988年 | 18篇 |
1987年 | 21篇 |
1986年 | 14篇 |
1985年 | 18篇 |
1984年 | 20篇 |
1983年 | 29篇 |
1982年 | 17篇 |
1981年 | 8篇 |
1980年 | 9篇 |
1979年 | 13篇 |
1978年 | 7篇 |
1977年 | 11篇 |
1974年 | 6篇 |
1973年 | 6篇 |
1972年 | 7篇 |
排序方式: 共有4079条查询结果,搜索用时 296 毫秒
51.
Tetsuya Kawai Iwase Kazuhiko Noriko Takaya Yuko Yamaguchi Ryuta Kishii Yasushi Kohno Haruaki Kurasaki 《Bioorganic & medicinal chemistry letters》2017,27(4):1045-1049
We attempted to optimize sulfonamide-based non-alkyne LpxC inhibitors by focusing on improvements in enzyme inhibitory and antibacterial activity. It was discovered that inhibitors possessing 2-aryl benzofuran as a hydrophobe exhibited good activity. In particular, compound 21 displayed impressive antibacterial activity (E. coli MIC = 0.063 μg/mL, K. pneumoniae MIC = 0.5 μg/mL, and P. aeruginosa MIC = 0.5 μg/mL), and is a promising lead for further exploration as an antibacterial agent. 相似文献
52.
Yuko?T. Sato Shun Watanabe Takahiro Kenmotsu Masatoshi Ichikawa Yuko Yoshikawa Jun Teramoto Tadayuki Imanaka Akira Ishihama Kenichi Yoshikawa 《Biophysical journal》2013,105(4):1037-1044
The effects of nucleoid proteins Fis and Dps of Escherichia coli on the higher order structure of a giant DNA were studied, in which Fis and Dps are known to be expressed mainly in the exponential growth phase and stationary phase, respectively. Fis causes loose shrinking of the higher order structure of a genome-sized DNA, T4 DNA (166 kbp), in a cooperative manner, that is, the DNA conformational transition proceeds through the appearance of a bimodal size distribution or the coexistence of elongated coil and shrunken globular states. The effective volume of the loosely shrunken state induced by Fis is 30–60 times larger than that of the compact state induced by spermidine, suggesting that cellular enzymes can access for DNA with the shrunken state but cannot for the compact state. Interestingly, Dps tends to inhibit the Fis-induced shrinkage of DNA, but promotes DNA compaction in the presence of spermidine. These characteristic effects of nucleotide proteins on a giant DNA are discussed by adopting a simple theoretical model with a mean-field approximation. 相似文献
53.
54.
55.
56.
Shoko Nakano Yuko Abe Kimiko Nakajima Shigetoshi Sano Osamu Yamamoto Kazumasa Wakamatsu Shosuke Ito Masahiro Hayashi Tamio Suzuki 《Pigment cell & melanoma research》2021,34(1):101-110
Post‐inflammatory hyperpigmentation (PIH) is a common cutaneous condition that can cause a disfigured appearance. However, the pathophysiology of PIH remains poorly understood, at least in part, because an appropriate animal model for research has not been established. In order to analyze the pathomechanism of PIH, we successfully induced PIH in a hairless version of transgenic mice (hk14‐SCF Tg/HRM) that have a human‐type epidermis containing melanin by repeated hapten application of 2,4‐dinitrofluorobenzene. Histopathologic observation showed epidermal hyperplasia, predominant infiltrations of inflammatory cells, and melanin‐containing cells in the dermis just after elicitation of the atopic dermatitis‐like condition. At week 2, the findings were similar to the characteristics of PIH, that is, an increase of melanin without spongiosis or liquid degeneration in the epidermis and an increase in dermal melanophages. Dynamic analysis of melanin showed that the melanin in the dermis remained for a longer duration than in the epidermis. Furthermore, immunohistochemical staining revealed that the majority of cells containing melanin were positive for the anti‐CD68 antibody, but negative for the anti‐F4/80 antibody. These data suggest that novel treatments of PIH should be targeted against macrophages and should eventually lead to the development of new treatment modalities. 相似文献
57.
Hiroaki Horikawa Midori Okada Yuko Nakamura Azusa Sato Noriko Iwamoto 《Free radical research》2013,47(10):1059-1065
The chemical properties of Amadori compounds in the presence of transition metal ions were studied, using the analogs 1-deoxy-1- n -butylamino- d -fructose (DBF) and N f -formyl-fructoselysine (fFL). The following characteristics were revealed: (a) DBF combined easily with Cu 2+ (but no other transition metal ions) to form a DBF-Cu 2+ complex in phosphate buffer, pH 7.4; (b) the complex was unstable, and degraded with the release of Cu + during incubation at 37°C; (c) degradation of the complex was associated with the production of hydroxyl radicals by the Fenton reaction and f -dicarbonyl compounds by non-autoxidative degradation; and (d) properties of DBF were similar to those of fFL. The above properties were additionally observed in glycated poly-Lys (GPL). Our findings indicate a novel mechanism for the generation of hydroxyl radicals and f -dicarbonyl compounds from Amadori adducts in the presence of Cu 2+ . 相似文献
58.
Nobuo N Noda Yuko Fujioka Takao Hanada Yoshinori Ohsumi Fuyuhiko Inagaki 《EMBO reports》2013,14(2):206-211
Atg12 is conjugated to Atg5 through enzymatic reactions similar to ubiquitination. The Atg12–Atg5 conjugate functions as an E3‐like enzyme to promote lipidation of Atg8, whereas lipidated Atg8 has essential roles in both autophagosome formation and selective cargo recognition during autophagy. However, the molecular role of Atg12 modification in these processes has remained elusive. Here, we report the crystal structure of the Atg12–Atg5 conjugate. In addition to the isopeptide linkage, Atg12 forms hydrophobic and hydrophilic interactions with Atg5, thereby fixing its position on Atg5. Structural comparison with unmodified Atg5 and mutational analyses showed that Atg12 modification neither induces a conformational change in Atg5 nor creates a functionally important architecture. Rather, Atg12 functions as a binding module for Atg3, the E2 enzyme for Atg8, thus endowing Atg5 with the ability to interact with Atg3 to facilitate Atg8 lipidation. 相似文献
59.
Yorishige Imamura Toshihisa Koga Hideaki Shimada Masaki Otagiri 《Journal of enzyme inhibition and medicinal chemistry》2013,28(1):35-39
The chemical modifications of rabbit liver carbonyl reductase (RLCR) with phenylglyoxal (PGO) and 2,3,4-trinitrobenzenesulfonate sodium (TNBS), which are respective chemical modifiers of arginine and lysine residues, were examined. RLCR was rapidly inactivated by these modifiers. Kinetic data for the inactivation demonstrated that each one of arginine and lysine residues is essential for catalytic activity of the enzyme. Furthermore, based on the protective effects of NADP +, NAD + and their constituents against the inactivation of RLCR by PGO and TNBS, we propose the possibility that the functional arginine and lysine residues are located in the coenzyme-binding domain of RLCR and interact with the 2′-phosphate group of NADPH. 相似文献
60.
Sachiko N. Isobe Hideki Hirakawa Shusei Sato Fumi Maeda Masami Ishikawa Toshiki Mori Yuko Yamamoto Kenta Shirasawa Mitsuhiro Kimura Masanobu Fukami Fujio Hashizume Tomoko Tsuji Shigemi Sasamoto Midori Kato Keiko Nanri Hisano Tsuruoka Chiharu Minami Chika Takahashi Tsuyuko Wada Akiko Ono Kumiko Kawashima Naomi Nakazaki Yoshie Kishida Mitsuyo Kohara Shinobu Nakayama Manabu Yamada Tsunakazu Fujishiro Akiko Watanabe Satoshi Tabata 《DNA research》2013,20(1):79-92