全文获取类型
收费全文 | 316篇 |
免费 | 17篇 |
出版年
2023年 | 2篇 |
2022年 | 5篇 |
2021年 | 11篇 |
2020年 | 8篇 |
2019年 | 8篇 |
2018年 | 9篇 |
2017年 | 8篇 |
2016年 | 12篇 |
2015年 | 19篇 |
2014年 | 17篇 |
2013年 | 27篇 |
2012年 | 19篇 |
2011年 | 30篇 |
2010年 | 16篇 |
2009年 | 12篇 |
2008年 | 21篇 |
2007年 | 12篇 |
2006年 | 15篇 |
2005年 | 17篇 |
2004年 | 4篇 |
2003年 | 8篇 |
2002年 | 6篇 |
2001年 | 6篇 |
2000年 | 10篇 |
1999年 | 2篇 |
1998年 | 3篇 |
1997年 | 1篇 |
1996年 | 1篇 |
1995年 | 2篇 |
1994年 | 3篇 |
1993年 | 1篇 |
1991年 | 2篇 |
1989年 | 4篇 |
1988年 | 2篇 |
1984年 | 7篇 |
1975年 | 1篇 |
1967年 | 1篇 |
1958年 | 1篇 |
排序方式: 共有333条查询结果,搜索用时 156 毫秒
111.
Residuals for multinomial models 总被引:1,自引:0,他引:1
112.
Qiongyu Hao Piwen Wang Pranabananda Dutta Seyung Chung Qun Li Kun Wang Jieqing Li Wei Cao Wenhong Deng Qing Geng Katrina Schrode Magda Shaheen Ke Wu Donghui Zhu Qiao-Hong Chen Guanglin Chen Yahya Elshimali Jay Vadgama Yong Wu 《Cell death & disease》2020,11(12)
The abnormal PI3K/AKT/mTOR pathway is one of the most common genomic abnormalities in breast cancers including triple-negative breast cancer (TNBC), and pharmacologic inhibition of these aberrations has shown activity in TNBC patients. Here, we designed and identified a small-molecule Comp34 that suppresses both AKT and mTOR protein expression and exhibits robust cytotoxicity towards TNBC cells but not nontumorigenic normal breast epithelial cells. Mechanically, long noncoding RNA (lncRNA) .1-204 (also named as NUDT3-AS4) acts as a microRNA sponge to compete with AKT1/mTOR mRNAs for binding to miR-99s, leading to decrease in degradation of AKT1/mTOR mRNAs and subsequent increase in AKT1/mTOR protein expression. Inhibition of lncRNA-NUDT3-AS4 and suppression of the NUDT3-AS4/miR-99s association contribute to Comp34-affected biologic pathways. In addition, Comp34 alone is effective in cells with secondary resistance to rapamycin, the best-known inhibitor of mTOR, and displays a greater in vivo antitumor efficacy and lower toxicity than rapamycin in TNBC xenografted models. In conclusion, NUDT3-AS4 may play a proproliferative role in TNBC and be considered a relevant therapeutic target, and Comp34 presents promising activity as a single agent to inhibit TNBC through regulation of NUDT3-AS4 and miR-99s.Subject terms: AL354740Drug discovery, Diseases 相似文献
113.
Amna Kashif Shaheen Hwang You Jin Park Jae Kweon 《Bioprocess and biosystems engineering》2018,41(11):1611-1620
Bioprocess and Biosystems Engineering - Microalgae Tetraselmis species were used to evaluate the biological characteristics of water-soluble polysaccharides (WSPs) as one of the significant... 相似文献
114.
Matthew F. Buas Lynn Onstad David M. Levine Harvey A. Risch Wong-Ho Chow Geoffrey Liu Rebecca C. Fitzgerald Leslie Bernstein Weimin Ye Nigel C. Bird Yvonne Romero Alan G. Casson Douglas A. Corley Nicholas J. Shaheen Anna H. Wu Marilie D. Gammon Brian J. Reid Laura J. Hardie Ulrike Peters David C. Whiteman Thomas L. Vaughan 《PloS one》2015,10(6)
115.
Aliah F. Shaheen Coralie Villa Yen-Ni Lee Anthony M.J. Bull Caroline M. Alexander 《Journal of electromyography and kinesiology》2013,23(2):326-333
BackgroundScapular taping is frequently used in the management of shoulder pain and as a part of injury prevention strategies in sports. It is believed to alter scapular kinematics and restore normal motion. However, there is little evidence to support its use. The aim of the study was to investigate the effect of shoulder taping on the scapular kinematics of asymptomatic subjects.MethodThirteen asymptomatic subjects performed elevations in the sagittal and scapular planes with no tape and after the application of tape. A motion tracking system and a scapula locator method were used to measure the shoulder movement. Co-ordinate frames were defined for the thorax, humerus and scapula and Euler angles were used to calculate joints rotations.ResultsScapular taping increased the scapular external and upward rotations and posterior tilt in elevations in the sagittal plane (p < 0.001). In the scapular plane, taping increased scapular external rotation (p < 0.05).ConclusionsTaping affects scapulothoracic kinematics in asymptomatic subjects. The effect may be different for different planes of movement. The findings have implications on the use of taping as a preventive measure in high-risk groups. Further work is needed to assess the effect of taping on symptomatic populations. 相似文献
116.
SO Akarca-Dizakar H Aktuğ F Oltulu G Öktem A Yavaşoğlu E Açikgöz 《Biotechnic & histochemistry》2013,88(5):328-335
Diabetes mellitus (DM) affects many organs including kidney. Tyrosine kinase can cause hypoglycemia and sunitinib is an inhibitor of tyrosine kinase. We investigated the possible effects of sunitinib on the kidney of streptozotocin (STZ) induced type 1 diabetic mice. We used 28 CD 1 type male mice divided into four groups of seven. Type 1 diabetes was induced by injection of STZ. Group 1 was the untreated control. Group 2 comprised non-diabetic mice + sunitinib. Both groups 1 and 2 exhibited normal blood glucose levels. Group 3 comprised STZ treated diabetic mice + saline. Group 4 were diabetic mice + sunitinib treatment. Kidneys were removed after 8 weeks. The immunoreactivities of vimentin, E-cadherin and S100 were assessed. Immunostaining of vimentin, E-cadherin and S100 was located in both the glomeruli and tubules of the kidney. We found that the number of vimentin and E-cadherin positive glomeruli and tubules were increased after sunitinib treatment compared to saline treated diabetic mice. The number of vimentin labeled tubules was decreased in the sunitinib treated group compared to diabetic + saline groups. Differences in the number of S100 positive tubules and glomeruli between groups 3 and 4 were not statistically significant. The effect of sunitinib on experimental diabetic mice appears to be related to levels of vimentin, E-cadherin and S100 in the glomeruli and tubules of the kidney, and sunitinib may protect against renal damage from DM. 相似文献
117.
Manzoor Ahmad Waqar Ahmad Mansoor Ahmad Muhammad Zeeshan Obaidullah Farzana Shaheen 《Journal of enzyme inhibition and medicinal chemistry》2013,28(6):1018-1022
Two new aconitine-type norditerpenoid alkaloids 6-dehydroacetylsepaconitine (1) and 13-hydroxylappaconitine (2), along with three known norditerpenoid alkaloids lycoctonine, delphatine and lappaconitine were isolated from the roots of the Aconitum heterophyllum Wall. These compounds exhibited significant antibacterial activity. The structure of compound 1 and 2 were deduced on the basis of their spectral data. 相似文献
118.
Mohsin Khan Sadia Mohsin Shaheen N. Khan Sheikh Riazuddin 《Journal of cellular and molecular medicine》2011,15(7):1515-1527
Myocardial infarction is one of the leading causes of mortality in aged people. Whether age of donors of mesenchymal stem cells (MSCs) affects its ability to repair the senescent heart tissue is unknown. In the present study, MSCs from young (2 months) and aged (18 months) green fluorescent protein expressing C57BL/6 mice were characterized with p16INK4a and β‐gal associated senescence. Myocardial infarction was produced in 18‐month‐old wild‐type C57BL/6 mice transplanted with MSCs from young and aged animals in the border of the infarct region. Expression of p16INK4a in MSCs from aged animals was significantly higher (21.5%± 1.2, P < 0.05) as compared to those from young animals (9.2%± 2.8). A decline in the tube‐forming ability on Matrigel was also observed in aged MSCs as well as down‐regulation of insulin‐like growth factor‐1, fibroblast growth factor (FGF‐2), vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) compared to young cells. Mice transplanted with young MSCs exhibited significant improvement in their left ventricle (LV) systolic and diastolic function as demonstrated by dp/dtmax, dp/dtmin, Pmax. Reduction in the LV fibrotic area was concomitant with neovascularization as demonstrated by CD31 and smooth muscle actin (SMA) expression. Real‐time RT‐PCR analysis for VEGF, stromal cell derived factor (SDF‐1α) and GATA binding factor 4 (GATA‐4) genes further confirmed the effect of age on MSC differentiation towards cardiac lineages and enhanced angiogenesis. These studies lead to the conclusion that repair potential of MSCs is dependent on the age of donors and the repair of senescent infarcted myocardium requires young healthy MSCs. 相似文献
119.
Kuettel S Greenwald J Kostrewa D Ahmed S Scapozza L Perozzo R 《PLoS neglected tropical diseases》2011,5(5):e1164
Background
The essential purine salvage pathway of Trypanosoma brucei bears interesting catalytic enzymes for chemotherapeutic intervention of Human African Trypanosomiasis. Unlike mammalian cells, trypanosomes lack de novo purine synthesis and completely rely on salvage from their hosts. One of the key enzymes is adenosine kinase which catalyzes the phosphorylation of ingested adenosine to form adenosine monophosphate (AMP) utilizing adenosine triphosphate (ATP) as the preferred phosphoryl donor.Methods and Findings
Here, we present the first structures of Trypanosoma brucei rhodesiense adenosine kinase (TbrAK): the structure of TbrAK in complex with the bisubstrate inhibitor P1,P5-di(adenosine-5′)-pentaphosphate (AP5A) at 1.55 Å, and TbrAK complexed with the recently discovered activator 4-[5-(4-phenoxyphenyl)-2H-pyrazol-3-yl]morpholine (compound 1) at 2.8 Å resolution.Conclusions
The structural details and their comparison give new insights into substrate and activator binding to TbrAK at the molecular level. Further structure-activity relationship analyses of a series of derivatives of compound 1 support the observed binding mode of the activator and provide a possible mechanism of action with respect to their activating effect towards TbrAK. 相似文献120.