全文获取类型
收费全文 | 26594篇 |
免费 | 1807篇 |
国内免费 | 1072篇 |
出版年
2024年 | 34篇 |
2023年 | 239篇 |
2022年 | 544篇 |
2021年 | 992篇 |
2020年 | 697篇 |
2019年 | 873篇 |
2018年 | 1098篇 |
2017年 | 793篇 |
2016年 | 1174篇 |
2015年 | 1404篇 |
2014年 | 1654篇 |
2013年 | 1990篇 |
2012年 | 2179篇 |
2011年 | 2103篇 |
2010年 | 1286篇 |
2009年 | 1069篇 |
2008年 | 1456篇 |
2007年 | 1362篇 |
2006年 | 1284篇 |
2005年 | 1139篇 |
2004年 | 922篇 |
2003年 | 927篇 |
2002年 | 768篇 |
2001年 | 545篇 |
2000年 | 454篇 |
1999年 | 398篇 |
1998年 | 246篇 |
1997年 | 160篇 |
1996年 | 124篇 |
1995年 | 133篇 |
1994年 | 97篇 |
1993年 | 84篇 |
1992年 | 107篇 |
1991年 | 115篇 |
1990年 | 99篇 |
1989年 | 77篇 |
1988年 | 64篇 |
1987年 | 69篇 |
1986年 | 50篇 |
1985年 | 69篇 |
1984年 | 43篇 |
1983年 | 39篇 |
1982年 | 36篇 |
1981年 | 27篇 |
1980年 | 22篇 |
1979年 | 38篇 |
1978年 | 36篇 |
1977年 | 34篇 |
1972年 | 24篇 |
1952年 | 40篇 |
排序方式: 共有10000条查询结果,搜索用时 125 毫秒
981.
Hongmei Zhu Wenke Li Zhuole Wang Jianguo Chen Mingxing Ding Li Han 《Microbial biotechnology》2019,12(6):1337-1345
Endometritis, which is usually caused by bacterial infection, is characterized by high levels of pro-inflammatory cytokines and a high infertility rate. Triggering receptor expressed on myeloid cells-1 (TREM-1) has been recognized as a potent amplifier of inflammatory reactions. Studies have demonstrated reduced inflammatory responses and mortality rates of animals with bacterial infection due to the blocking of TREM-1 expression. However, whether TREM-1 deficiency could alleviate the inflammatory reaction in bacterial endometritis is still unclear. Here, TREM-1 knock-out (Trem-1−/−) mice were used to inhibit TREM-1 signalling to evaluate its role in inflammatory reactions after a highly pathogenic LPS infection in mice uteri. The results demonstrated that TREM-1 deficiency attenuated the inflammation in mice uteri; markedly reduced the number of polymorphonuclear neutrophils; and suppressed interleukin-1β (IL-1β), IL-6, and tumour necrosis factor-α (TNF-α) concentrations in serum as well as their production in inflamed uteri after LPS stimulation. Our results illustrate an anticipated pathogenic impact of TREM-1 on endometritis during LPS infection and indicate that blocking of TREM-1 in LPS-induced endometritis holds considerable promise for blunting excessive inflammation. 相似文献
982.
Meixia Zhang Yan Luo Zhengbing Yan Jiao Chen Anwar Eziz Kaihui Li Wenxuan Han 《Journal of Plant Ecology》2019,12(2):358
Aims
We aim to investigate variations in the resorption efficiencies of 10 mineral nutrients [i.e. nitrogen (N), phosphorus (P), potassium (K), magnesium (Mg), calcium (Ca), manganese (Mn), zinc (Zn), aluminum (Al), iron (Fe) and copper (Cu)] in leaves of desert shrubs and to explore effects of aridity on resorption efficiency of these nutrients. 相似文献
983.
Jia Jin Xiaoqing Ye Derrick Boateng Kaili Dai Fei Ye Pengfei Du Han Yu 《Bioorganic & medicinal chemistry letters》2019,29(16):2358-2363
Protein tyrosine phosphatase 1B (PTP1B) plays an important role in the negative regulation of insulin and leptin signaling. The development of small molecular inhibitors targeting PTP1B has been validated as a potential therapeutic strategy for Type 2 diabetes (T2D). In this work, we have identified a series of compounds containing dihydropyridine thione and particular chiral structure as novel PTP1B inhibitors. Among those, compound 4b showed moderate activity with IC50 value of 3.33 μM and meanwhile with good selectivity (>30-fold) against TCPTP. The further MOA study of PTP1B demonstrated that compounds 4b is a substrate-competitive inhibitor. The binding mode analysis suggested that compound 4b simultaneously occupies the active site and the second phosphotyrosine (pTyr) binding site of PTP1B. Furthermore, the cell viability assay of compound 4b showed tolerable cytotoxicity in L02 cells, thus 4b may be prospectively used to further in vivo study. 相似文献
984.
Kai Cheng Shiyu Li Xiao Lv Yongbin Tian Haiyan Kong Xufeng Huang Yajun Duan Jihong Han Zhouling Xie Chenzhong Liao 《Bioorganic & medicinal chemistry letters》2019,29(8):1012-1018
Herein we report our efforts of developing reversible selective hMAO-B inhibitors based on isatin, a fragment in an X-ray crystal structure. Five different scaffolds were designed and many compounds were synthesized. Among them, compound A3 demonstrated very high potency and isoform selectivity against hMAO-B, 11 and 13 times more potent (IC50?=?3?nM) and 23.64 and 6.8 times more selective than the marked drugs, selegiline and safinamide. However, the endeavors to modify the polar 3-one group of isatin, that is in a hydrophobic environment in the binding site of hMAO-B, to small nonpolar hydrophobic groups did not bring about improved hMAO-B inhibitors, which may challenge our understanding of molecular interactions and molecular recognition in biological systems. 相似文献
985.
Dorota Żelaszczyk Magdalena Jakubczyk Karolina Pytka Anna Rapacz Maria Walczak Paulina Janiszewska Katarzyna Pańczyk Paweł Żmudzki Karolina Słoczyńska Henryk Marona Anna M. Waszkielewicz 《Bioorganic & medicinal chemistry letters》2019,29(21):126679
Searching for CNS active cyclic amines derivatives containing heterocyclic xanthone core we designed and synthesized a set of fourteen novel 2- or 4-methylxanthone substituted by alkyl- or aryl-piperazine moieties. The compounds were evaluated in vivo for their potential antidepressant-like activity (in the forced swim test) and anxiolytic-like activity (four-plate test) and their inhibitory effect against rat 5-HT2 receptor was checked. The pharmacokinetic analysis of active compounds done by a non-compartmental approach have shown a rapid absorption of all studied molecules from intraperitoneal cavity and good penetration the blood-brain barrier after i.p. administration with brain to plasma ratios varied from 2.8 to 31.6. Genotoxicity and biotransformation of active compounds were studied. Compound 19 interactions with major classes of GPCRs, uptake systems and ion channels were tested and results indicated that it binds to 5-HT2A, 5-HT2B receptors and sodium channels. 相似文献
986.
987.
988.
SAR inspired by aldehyde oxidase (AO) metabolism: Discovery of novel,CNS penetrant tricyclic M4 PAMs
Trevor C. Chopko Changho Han Alison R. Gregro Darren W. Engers Andrew S. Felts Mike S. Poslusney Katrina A. Bollinger Ryan D. Morrison Michael Bubser Atin Lamsal Vincent B. Luscombe Hyekyung P. Cho Nathalie C. Schnetz-Boutaud Alice L. Rodriguez Sichen Chang J. Scott Daniels Donald F. Stec Colleen M. Niswender Bruce J. Melancon 《Bioorganic & medicinal chemistry letters》2019,29(16):2224-2228
This letter describes progress towards an M4 PAM preclinical candidate inspired by an unexpected aldehyde oxidase (AO) metabolite of a novel, CNS penetrant thieno[2,3-c]pyridine core to an equipotent, non-CNS penetrant thieno[2,3-c]pyrdin-7(6H)-one core. Medicinal chemistry design efforts yielded two novel tricyclic cores that enhanced M4 PAM potency, regained CNS penetration, displayed favorable DMPK properties and afforded robust in vivo efficacy in reversing amphetamine-induced hyperlocomotion in rats. 相似文献
989.