全文获取类型
收费全文 | 1716篇 |
免费 | 83篇 |
国内免费 | 1篇 |
出版年
2023年 | 10篇 |
2022年 | 25篇 |
2021年 | 43篇 |
2020年 | 24篇 |
2019年 | 27篇 |
2018年 | 44篇 |
2017年 | 40篇 |
2016年 | 61篇 |
2015年 | 97篇 |
2014年 | 106篇 |
2013年 | 153篇 |
2012年 | 158篇 |
2011年 | 137篇 |
2010年 | 97篇 |
2009年 | 84篇 |
2008年 | 80篇 |
2007年 | 91篇 |
2006年 | 86篇 |
2005年 | 67篇 |
2004年 | 47篇 |
2003年 | 56篇 |
2002年 | 48篇 |
2001年 | 16篇 |
2000年 | 14篇 |
1999年 | 15篇 |
1998年 | 8篇 |
1997年 | 8篇 |
1996年 | 7篇 |
1995年 | 7篇 |
1994年 | 5篇 |
1993年 | 7篇 |
1992年 | 18篇 |
1991年 | 10篇 |
1990年 | 13篇 |
1989年 | 4篇 |
1988年 | 5篇 |
1987年 | 11篇 |
1986年 | 7篇 |
1985年 | 4篇 |
1983年 | 7篇 |
1982年 | 4篇 |
1981年 | 4篇 |
1980年 | 4篇 |
1979年 | 3篇 |
1978年 | 4篇 |
1975年 | 3篇 |
1974年 | 5篇 |
1967年 | 3篇 |
1966年 | 3篇 |
1959年 | 2篇 |
排序方式: 共有1800条查询结果,搜索用时 20 毫秒
71.
Riyaj S. Tamboli Rajani Giridhar Hardik P. Gandhi Ashish M. Kanhed Hemant M. Mande 《Journal of enzyme inhibition and medicinal chemistry》2016,31(5):704-713
The aim of this research work was to investigate a series of novel 5,6-diaryl-1,2,4-triazines (3a–3q) containing 3-morpholinoethylamine side chain, and to address their antiplatelet activity by in vitro, ex vivo and in vivo methods. All compounds were synthesized by environment benign route and their structures were unambiguously confirmed by spectral data. Compounds (3l) and (3m) were confirmed by their single crystal X-ray structures. Out of all the synthesized compounds, 10 were found to be more potent in vitro than aspirin; six of them were found to be prominent in ex vivo assays and one compound (3d) was found to have the most promising antithrombotic profile in vivo. Moreover, compound (3d) demonstrated less ulcerogenicity in rats as compared to aspirin. The selectivity of the most promising compound (3d) for COX-1 and COX-2 enzymes was determined with the help of molecular docking studies and the results were correlated with the biological activity. 相似文献
72.
Ajay Pazhayattil Daniel Alsmeyer Shu Chen Maksuda Hye Marzena Ingram Pradeep Sanghvi 《AAPS PharmSciTech》2016,17(4):829-833
The approach documented in this article reviews data from earlier process validation lifecycle stages with a described statistical model to provide the “best estimate” on the number of process performance qualification (PPQ) batches that should generate sufficient information to make a scientific and risk-based decision on product robustness. This approach is based upon estimation of a statistical confidence from the current product knowledge (Stage 1), historical variability for similar products/processes (batch-to-batch), and label claim specifications such as strength. The analysis is to determine the confidence level with the measurements of the product quality attributes and to compare them with the specifications. The projected minimum number of PPQ batches required will vary depending on the product, process understanding, and attributes, which are critical input parameters for the current statistical model. This new approach considers the critical finished product CQAs (assay, dissolution, and content uniformity), primarily because assay/content uniformity and dissolution as well as strength are the components of the label claim. The key CQAs determine the number of PPQ batches. This approach will ensure that sufficient scientific data is generated to demonstrate process robustness as desired by the 2011 FDA guidance. 相似文献
73.
74.
75.
76.
Angela M. Mech Kathryn A. Thomas Travis D. Marsico Daniel A. Herms Craig R. Allen Matthew P. Ayres Kamal J. K. Gandhi Jessica Gurevitch Nathan P. Havill Ruth A. Hufbauer Andrew M. Liebhold Kenneth F. Raffa Ashley N. Schulz Daniel R. Uden Patrick C. Tobin 《Ecology and evolution》2019,9(21):12216-12230
- 相似文献
77.
78.
79.
Chaturvedi P Singh AP Moniaux N Senapati S Chakraborty S Meza JL Batra SK 《Molecular cancer research : MCR》2007,5(4):309-320
MUC4, a transmembrane mucin, is aberrantly expressed in pancreatic adenocarcinomas while remaining undetectable in the normal pancreas. Recent studies have shown that the expression of MUC4 is associated with the progression of pancreatic cancer and is inversely correlated with the prognosis of pancreatic cancer patients. In the present study, we have examined the phenotypic and molecular consequences of MUC4 silencing with an aim of establishing the mechanistic basis for its observed role in the pathogenesis of pancreatic cancer. The silencing of MUC4 expression was achieved by stable expression of a MUC4-specific short hairpin RNA in CD18/HPAF, a highly metastatic pancreatic adenocarcinoma cell line. A significant decrease in MUC4 expression was detected in MUC4-knockdown (CD18/HPAF-siMUC4) cells compared with the parental and scrambled short interfering RNA-transfected (CD18/HPAF-Scr) control cells by immunoblot analysis and immunofluorescence confocal microscopy. Consistent with our previous observation, inhibition of MUC4 expression restrained the pancreatic tumor cell growth and metastasis as shown in an orthotopic mouse model. Our in vitro studies revealed that MUC4-associated increase in tumor cell growth resulted from both the enhanced proliferation and reduced cell death. Furthermore, MUC4 expression was also associated with significantly increased invasiveness (P < or = 0.05) and changes in actin organization. The presence of MUC4 on the cell surface was shown to interfere with the tumor cell-extracellular matrix interactions, in part, by inhibiting the integrin-mediated cell adhesion. An altered expression of growth- and metastasis-associated genes (LI-cadherin, CEACAM6, RAC1, AnnexinA1, thrombomodulin, epiregulin, S100A4, TP53, TP53BP, caspase-2, caspase-3, caspase-7, plakoglobin, and neuregulin-2) was also observed as a consequence of the silencing of MUC4. In conclusion, our study provides experimental evidence that supports the functional significance of MUC4 in pancreatic cancer progression and indicates a novel role for MUC4 in cancer cell signaling. 相似文献
80.
Ralf Buettner Le Xuan Truong Nguyen Bijender Kumar Corey Morales Chao Liu Lisa S. Chen Tea Pemovska Timothy W. Synold Joycelynne Palmer Ryan Thompson Ling Li Dinh Hoa Hoang Bin Zhang Lucy Ghoda Claudia Kowolik Mika Kontro Calum Leitch Krister Wennerberg Xiaochun Yu Ching-Cheng Chen David Horne Varsha Gandhi Vinod Pullarkat Guido Marcucci Steven T. Rosen 《Journal of cellular physiology》2019,234(9):16295-16303