全文获取类型
收费全文 | 2902篇 |
免费 | 114篇 |
国内免费 | 2篇 |
专业分类
3018篇 |
出版年
2023年 | 7篇 |
2022年 | 23篇 |
2021年 | 45篇 |
2020年 | 27篇 |
2019年 | 35篇 |
2018年 | 58篇 |
2017年 | 46篇 |
2016年 | 49篇 |
2015年 | 121篇 |
2014年 | 132篇 |
2013年 | 225篇 |
2012年 | 199篇 |
2011年 | 232篇 |
2010年 | 114篇 |
2009年 | 126篇 |
2008年 | 189篇 |
2007年 | 179篇 |
2006年 | 149篇 |
2005年 | 179篇 |
2004年 | 186篇 |
2003年 | 162篇 |
2002年 | 142篇 |
2001年 | 18篇 |
2000年 | 16篇 |
1999年 | 24篇 |
1998年 | 44篇 |
1997年 | 38篇 |
1996年 | 22篇 |
1995年 | 22篇 |
1994年 | 21篇 |
1993年 | 17篇 |
1992年 | 19篇 |
1991年 | 16篇 |
1990年 | 14篇 |
1989年 | 17篇 |
1988年 | 5篇 |
1987年 | 19篇 |
1986年 | 5篇 |
1985年 | 6篇 |
1984年 | 13篇 |
1983年 | 8篇 |
1982年 | 6篇 |
1981年 | 9篇 |
1980年 | 7篇 |
1979年 | 3篇 |
1977年 | 6篇 |
1976年 | 3篇 |
1975年 | 3篇 |
1974年 | 3篇 |
1973年 | 4篇 |
排序方式: 共有3018条查询结果,搜索用时 0 毫秒
81.
Li A Itoh T Taguchi T Xiang T Ebizuka Y Ichinose K 《Bioorganic & medicinal chemistry》2005,13(24):6856-6863
Medermycin shows the same trans (3S,15R) configuration as actinorhodin in the pyran ring crucial for its bioactivity. One medermycin biosynthetic gene, med-ORF12, is assumed to be involved in the stereochemical control at C-3. Functional complementation suggested that it plays a similar role as actVI-ORF1 previously proved to determine the stereospecificity at C-3 in actinorhodin biosynthesis. Co-expression of med-ORF12 with actinorhodin early biosynthetic genes further demonstrated that med-ORF12 encodes a ketoreductase responsible for the enantioselective reduction at C-3 in the formation of the pyran ring. 相似文献
82.
Akane Sueki Kazuyuki Matsuda Chinami Iwashita Chiaki Taira Nau Ishimine Shohei Shigeto Kenji Kawasaki Mitsutoshi Sugano Hiroshi Yamamoto Takayuki Honda 《Biochemical and biophysical research communications》2014
Epithelial–mesenchymal transition (EMT) is associated with pulmonary fibrosis, including idiopathic pulmonary fibrosis (IPF). In this study, we investigated EMT of human pulmonary epithelial-derived cells (A549). A549 cells was either cultured by itself or co-cultured with THP-1 macrophages under normoxic (21% O2) and hypoxic (2% O2) conditions. We evaluated the presence of EMT by determining the expression of EMT markers, E-cadherin, vimentin, and fibronectin. To determine the role of TGF-β1 and IL-1β in EMT of the A549 cells, we analyzed the effects of blocking their activity with TGF-β1 inhibitor or IL-1β neutralizing antibody respectively. The A549 cells presented EMT when they were co-cultured with THP-1 macrophages. The EMT of the A549 cells co-cultured with THP-1 macrophages was exacerbated under hypoxia. In addition, the EMT were prevented by the addition of TGF-β1 type I receptor kinase inhibitor. The hypoxic condition increased the mRNA levels of TGF-β1 in A549 cells and THP-1 macrophages and that of IL-1β in THP-1 macrophages when each cells were co-cultured. Anti-IL-1β neutralizing antibody attenuated TGF-β1 secretion in co-culture media under hypoxic conditions. Thus, the IL-1β from THP-1 macrophages up-regulated the TGF-β1 from A549 cells and THP-1 macrophages, and then the TGF-β1 from both cells induced and promoted the EMT of A549 cells when they were co-cultured under hypoxia. Together, these results demonstrate that the interaction between type II pneumocytes and macrophages under hypoxia is necessary for the development of pulmonary fibrosis. 相似文献
83.
Steroidal glycoalkaloids (SGAs) are nitrogen-con-taining secondary metabolites of the Solanum species, which are known to have large chemical and bioactive diversity in nature. While recent effort and ... 相似文献
84.
85.
86.
Flies without Trehalose 总被引:2,自引:0,他引:2
Hiroko Matsuda Takayuki Yamada Miki Yoshida Takashi Nishimura 《The Journal of biological chemistry》2015,290(2):1244-1255
Living organisms adapt to environmental changes through metabolic homeostasis. Sugars are used primarily for the metabolic production of ATP energy and carbon sources. Trehalose is a nonreducing disaccharide that is present in many organisms. In insects, the principal hemolymph sugar is trehalose instead of glucose. As in mammals, hemolymph sugar levels in Drosophila are regulated by the action of endocrine hormones. Therefore, the mobilization of trehalose to glucose is thought to be critical for metabolic homeostasis. However, the physiological role of trehalose as a hemolymph sugar during insect development remains largely unclear. Here, we demonstrate that mutants of the trehalose-synthesizing enzyme Tps1 failed to produce trehalose as expected but survived into the late pupal period and died before eclosion. Larvae without trehalose grew normally, with a slight reduction in body size, under normal food conditions. However, these larvae were extremely sensitive to starvation, possibly due to a local defect in the central nervous system. Furthermore, Tps1 mutant larvae failed to grow on a low-sugar diet and exhibited severe growth defects on a low-protein diet. These diet-dependent phenotypes of Tps1 mutants demonstrate the critical role of trehalose during development in Drosophila and reveal how animals adapt to changes in nutrient availability. 相似文献
87.
88.
Kambe T Maruyama T Nakai Y Yoshida H Oida H Maruyama T Abe N Nishiura A Nakai H Toda M 《Bioorganic & medicinal chemistry》2012,20(7):2235-2251
To identify potent EP2/EP4 dual agonists with excellent subtype selectivity, a series of γ-lactam prostaglandin E analogs bearing a 16-phenyl ω-chain were synthesized and evaluated. Structural hybridization of 1 and 2, followed by more detailed chemical modification of the benzoic acid moiety, led us to the discovery of a 2-mercaptothiazole-4-carboxylic acid analog 3 as the optimal compound in the series. An isomer of this compound, the 2-mercaptothiazole-5-carboxylic acid analog 13, showed 34-fold and 13-fold less potent EP2 and EP4 receptor affinities, respectively. Structure activity relationship data from an in vitro mouse receptor binding assay are presented. Continued evaluation in an in vivo rat model of another 2-mercaptothiazole-4-carboxylic acid analog 17, optimized for sustained compound release from PLGA microspheres, demonstrated its effectiveness in a rat bone fracture-healing model following topical administration. 相似文献
89.
Tanaka K Yokoi S Morimoto K Iwata T Nakamoto Y Nakayama K Koyama K Fujiwara T Fukase K 《Bioorganic & medicinal chemistry》2012,20(6):1865-1868
Versatile method for living cell labeling has been established. Cell surfaces are initially biotinylated by azaelectrocyclization, and then treated with the fluorescence-labeled avidin or the anti-biotin antibody. 相似文献
90.
T Taguchi T Ebihara A Furukawa Y Hidaka R Ariga S Okamoto K Ichinose 《Bioorganic & medicinal chemistry letters》2012,22(15):5041-5045
An oxygenated derivative of dihydrokalafungin (DHK) was isolated from a deletion mutant of the actVA-ORF4 gene involved in the biosynthesis of a dimeric benzoisochromanequinone (BIQ) antibiotic, actinorhodin (ACT), in Streptomyces coelicolor A3(2). Spectroscopic analysis elucidated its structure as 8-hydroxy-DHK, corresponding to the monomeric unit of ACT. Further metabolite analysis identified its related compound, clearly derived from the reduction of 8-hydroxy-DHK. The structures of these metabolites indicate the essential role of ActVA-ORF4 in ACT biosynthesis, specifically in dimerization of a BIQ intermediate via C-C bond formation. 相似文献