全文获取类型
收费全文 | 6871篇 |
免费 | 699篇 |
国内免费 | 920篇 |
出版年
2024年 | 41篇 |
2023年 | 175篇 |
2022年 | 355篇 |
2021年 | 526篇 |
2020年 | 402篇 |
2019年 | 446篇 |
2018年 | 393篇 |
2017年 | 260篇 |
2016年 | 328篇 |
2015年 | 504篇 |
2014年 | 535篇 |
2013年 | 554篇 |
2012年 | 629篇 |
2011年 | 565篇 |
2010年 | 346篇 |
2009年 | 292篇 |
2008年 | 356篇 |
2007年 | 273篇 |
2006年 | 249篇 |
2005年 | 181篇 |
2004年 | 186篇 |
2003年 | 158篇 |
2002年 | 145篇 |
2001年 | 101篇 |
2000年 | 84篇 |
1999年 | 86篇 |
1998年 | 46篇 |
1997年 | 42篇 |
1996年 | 27篇 |
1995年 | 21篇 |
1994年 | 20篇 |
1993年 | 20篇 |
1992年 | 26篇 |
1991年 | 20篇 |
1990年 | 10篇 |
1989年 | 15篇 |
1988年 | 11篇 |
1987年 | 11篇 |
1986年 | 10篇 |
1985年 | 5篇 |
1984年 | 4篇 |
1983年 | 7篇 |
1981年 | 2篇 |
1979年 | 3篇 |
1978年 | 2篇 |
1976年 | 2篇 |
1974年 | 2篇 |
1973年 | 3篇 |
1969年 | 2篇 |
1967年 | 2篇 |
排序方式: 共有8490条查询结果,搜索用时 78 毫秒
991.
Yundong Xie Lihua Shao Qiutang Wang Yue Bai Zizhang Chen Na Li Yanhong Xu Yiping Li Guangde Yang Xiaoli Bian 《Bioorganic & medicinal chemistry letters》2018,28(23-24):3731-3735
Nitric oxide (NO) dysfunction has been found to be an important factor in both the development and progression of diabetic complications due to its many roles in the vascular system. Multifunctional compounds with hypoglycemic and endothelial protective action will be promising agents for the treatment of diabetes and its complications. In this study, a series of novel NO-donating sitagliptin derivatives and relevant metabolites were synthesized and evaluated as potential multifunctional hypoglycemic agents. All of synthetic compounds shown remarkable inhibitory activity against dipeptidyl peptidase IV (DPP-IV) in vitro and demonstrated excellent hypoglycemic activities in diabetic mice, similar to the activity of sitagliptin, and compounds T1-T4 shown different extents of NO-releasing abilities and potent antioxidant abilities in vivo. By screening in DPP-4, compound T4 was recognized as a potent DPP-4 inhibitor with the IC50 value of 0.060?μM. Docking study revealed compound T4 has a favorable binding mode. Furthermore, compounds T1-T4 exhibited different extents of NO-releasing abilities and excellent anti-platelet aggregation in vitro. The overall results suggested that T4 could help to the amelioration of endothelial dysfunction by reducing blood glucose, lessening oxidative stress and raising NO levels as well as inhibiting platelet aggregation. Based on this research, compound T4 deserves further investigation as potential new multifunctional anti-diabetic agent with antioxidant, anti-platelet aggregation and endothelial protective properties. 相似文献
992.
Zonghua Luo Xuyi Yue Hao Yang Hui Liu Robyn S. Klein Zhude Tu 《Bioorganic & medicinal chemistry letters》2018,28(3):488-496
Eleven new sphingosine 1-phosphate receptor 2 (S1PR2) ligands were synthesized by modifying lead compound N-(2,6-dichloropyridin-4-yl)-2-(4-isopropyl-1,3-dimethyl-1H-pyrazolo[3,4-b]pyridin-6-yl)hydrazine-1-carboxamide (JTE-013) and their binding affinities toward S1PRs were determined in vitro using [32P]S1P and cell membranes expressing recombinant human S1PRs. Among these ligands, 35a (IC50?=?29.1?±?2.6?nM) and 35b (IC50?=?56.5?±?4.0?nM) exhibit binding potency toward S1PR2 comparable to JTE-013 (IC50?=?58.4?±?7.4?nM) with good selectivity for S1PR2 over the other S1PRs (IC50?>?1000?nM). Further optimization of these analogues may identify additional and more potent and selective compounds targeting S1PR2. 相似文献
993.
Yin Jiang Hui-Ying Li Xiao-Hui Li Jun Lu Quan Zhang Cui-Gai Bai Yue Chen 《Bioorganic & medicinal chemistry letters》2018,28(4):737-741
Isothiocyanates 7a and 7b have poor stability and aqueous solubility. To address these problems, prodrugs 8a and 8b were synthesized. Prodrugs 8a and 8b were stable in HEPES buffer at pH 4.4, but released the active compounds 7a and 7b in HEPES buffer at pH 7.4 and in mouse plasma, respectively. Compound 8a and especially compound 8b showed anti-inflammatory effects. Compound 8b demonstrated significant efficacy in animal models of traumatic inflammation, acute inflammation and rheumatoid arthritis. Compound 8b also did not cause appreciable toxicity in mice after 5?weeks at a daily dose of 200?mg/kg. 相似文献
994.
Chen Shang Zhou Yue Zhou Lichun Guan Yanhui Zhang Yu Han Xiuzhen 《Molecular and cellular biochemistry》2018,448(1-2):225-235
Molecular and Cellular Biochemistry - Choroidal neovascularization (CNV) is the hallmark of late-staged wet age-related macular degeneration (AMD). Vascular endothelial growth factor (VEGF) is a... 相似文献
995.
Peng Zhao Ren-Yuan Chang Ning Liu Jing Wang Ru Zhou Xue Qi Yue Liu Lin Ma Yang Niu Tao Sun Yu-Xiang Li Yan-Ping He Jian-Qiang Yu 《Cellular and molecular neurobiology》2018,38(2):529-540
Oxysophocarpine (OSC), an alkaloid isolated from Sophora flavescens Ait, has been traditionally used as a medicinal agent based on the observed pharmacological effects. In this study, the direct effect of OSC against neuronal injuries induced by oxygen and glucose deprivation (OGD) in neonatal rat primary-cultured hippocampal neurons and its mechanisms were investigated. Cultured hippocampal neurons, which were exposed to OGD for 2 h followed by a 24 h reoxygenation, were used as an in vitro model of ischemia and reperfusion. 2-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and lactate dehydrogenase (LDH) assay were used to confirm neural damage and to further evaluate the protective effects of OSC. The concentration of intracellular-free calcium [Ca2+]i and mitochondrial membrane potential (MMP) were measured to determine the intracellular mechanisms and to further estimate the degree of neuronal damage. Changes in expression of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, p-ERK1/2, p-JNK1/2, and p-p38 MAPK were also observed in the in vitro model. It was shown that OSC (0.8, 2, or 5 µmol/L) significantly attenuated the increased absorbance of MTT, and the release of LDH manifests the neuronal damage by the OGD/R. Meanwhile, the pretreatment of the neurons during the reoxygenation period with OSC significantly increased MMP; it also inhibited [Ca2+]i the elevation in a dose-dependent manner. Furthermore, the pretreatment with OSC (0.8, 2, or 5 µmol/L) significantly down-regulated expressions of IL-1β, TNF-α, p-ERK1/2, p-JNK1/2, and p-p38 MAPK in neonatal rat primary-cultured hippocampal neurons induced by OGD/R injury. In conclusion, OSC displays a protective effect on OGD-injured hippocampal neurons by attenuating expression of inflammatory factors via down-regulated the MAPK signaling pathway. 相似文献
996.
997.
Gao Dawen Liu Fengqin Xie Yue Liang Hong 《Applied microbiology and biotechnology》2018,102(16):7195-7205
Applied Microbiology and Biotechnology - Ammonia-oxidizing archaea (AOA) and ammonia-oxidizing bacteria (AOB) contribute significantly to the nitrogen cycle. The community structure of AOA and AOB... 相似文献
998.
Ambuchi John Justo Zhang Zhaohan Dong Yue Huang Linlin Feng Yujie 《Applied microbiology and biotechnology》2018,102(16):7147-7158
Applied Microbiology and Biotechnology - The quest to understand and subsequently improve the role played by bacteria and archaea in the degradation of organic matter both in natural and engineered... 相似文献
999.
Formation of forest gaps accelerates C,N and P release from foliar litter during 4 years of decomposition in an alpine forest 总被引:1,自引:0,他引:1
Xiangyin Ni Björn Berg Wanqin Yang Han Li Shu Liao Bo Tan Kai Yue Zhenfeng Xu Li Zhang Fuzhong Wu 《Biogeochemistry》2018,137(3):321-336
High-latitude boreal and arctic surface/inland waters contain sizeable reservoirs of dissolved organic matter (DOM) and trace elements (TE), which are subject to seasonal freezing. Specifically, shallow ponds and lakes in the permafrost zone often freeze solid, which can lead to transformations in the colloidal and dissolved fractions of DOM and TE. Here, we present results from experimental freeze-thaw cycles using iron (Fe)- and DOM-rich water from thaw ponds situated in Stordalen and Storflaket palsa mires in northern Sweden. After ten cycles of freezing, 85% of Fe and 25% of dissolved organic carbon (DOC) were removed from solution in circumneutral fen water (pH 6.9) but a much smaller removal of Fe and DOC (< 7%) was found in acidic bog water (pH 3.6). This removal pattern was consistent with initial supersaturation of fen water with respect to Fe hydroxide and a lack of supersaturation with any secondary mineral phase in the bog water. There was a nearly two- to threefold increase in the low-molecular-weight (LMW) fraction of organic carbon (OC) and several TEs caused by the repeated freeze-thaw cycles. Future increases in the freeze-thaw frequency of surface waters with climate warming may remove up to 25% of DOC in circumneutral organic-rich waters. Furthermore, an increase of LMW OC may result in enhanced carbon dioxide losses from aquatic ecosystems since this fraction is potentially more susceptible to biodegradation. 相似文献
1000.