全文获取类型
收费全文 | 5357篇 |
免费 | 369篇 |
出版年
2023年 | 18篇 |
2022年 | 55篇 |
2021年 | 98篇 |
2020年 | 46篇 |
2019年 | 81篇 |
2018年 | 119篇 |
2017年 | 99篇 |
2016年 | 154篇 |
2015年 | 222篇 |
2014年 | 275篇 |
2013年 | 410篇 |
2012年 | 453篇 |
2011年 | 440篇 |
2010年 | 277篇 |
2009年 | 208篇 |
2008年 | 343篇 |
2007年 | 341篇 |
2006年 | 323篇 |
2005年 | 322篇 |
2004年 | 285篇 |
2003年 | 231篇 |
2002年 | 247篇 |
2001年 | 56篇 |
2000年 | 50篇 |
1999年 | 56篇 |
1998年 | 51篇 |
1997年 | 37篇 |
1996年 | 43篇 |
1995年 | 40篇 |
1994年 | 31篇 |
1993年 | 41篇 |
1992年 | 32篇 |
1991年 | 18篇 |
1990年 | 19篇 |
1989年 | 17篇 |
1988年 | 16篇 |
1987年 | 16篇 |
1986年 | 14篇 |
1985年 | 13篇 |
1984年 | 22篇 |
1983年 | 16篇 |
1982年 | 7篇 |
1981年 | 16篇 |
1980年 | 10篇 |
1979年 | 7篇 |
1978年 | 6篇 |
1977年 | 8篇 |
1975年 | 5篇 |
1974年 | 6篇 |
1965年 | 5篇 |
排序方式: 共有5726条查询结果,搜索用时 0 毫秒
901.
Evangelia E. Tsakiridis Lindsay Broadfield Katarina Marcinko Olga-Demetra Biziotis Amr Ali Bassem Mekhaeil Elham Ahmadi Kanwaldeep Singh Aruz Mesci Panayiotis G. Zacharidis Alexander E. Anagnostopoulos Tobias Berg Paola Muti Gregory R. Steinberg Theodoros Tsakiridis 《Translational oncology》2021,14(11):101209
BackgroundThere is need for well-tolerated therapies for prostate cancer (PrCa) secondary prevention and to improve response to radiotherapy (RT). The anti-diabetic agent metformin (MET) and the aspirin metabolite salicylate (SAL) are shown to activate AMP-activated protein kinase (AMPK), suppress de novo lipogenesis (DNL), the mammalian target of rapamycin (mTOR) pathway and reduce PrCa proliferation in-vitro. The purpose of this study was to examine whether combined MET+SAL treatment could provide enhanced PrCa tumor suppression and improve response to RT.MethodsAndrogen-sensitive (22RV1) and resistant (PC3, DU-145) PrCa cells and PC3 xenografts were used to examine whether combined treatment with MET+SAL can provide improved anti-tumor activity compared to each agent alone in non-irradiated and irradiated PrCa cells and tumors. Mechanisms of action were investigated with analysis of signaling events, mitochondria respiration and DNL activity assays.ResultsWe observed that PrCa cells are resistant to clinically relevant doses of MET. Combined MET + SAL treatment provides synergistic anti-proliferative activity at clinically relevant doses and enhances the anti-proliferative effects of RT. This was associated with suppression of oxygen consumption rate (OCR), activation of AMPK, suppression of acetyl-CoA carboxylase (ACC)-DNL and mTOR-p70s6k/4EBP1 and HIF1α pathways. MET + SAL reduced tumor growth in non-irradiated tumors and enhanced the effects of RT.ConclusionMET+SAL treatment suppresses PrCa cell proliferation and tumor growth and enhances responses to RT at clinically relevant doses. Since MET and SAL are safe, widely-used and inexpensive agents, these data support the investigation of MET+SAL in PrCa clinical trials alone and in combination with RT. 相似文献
902.
Sara Guariento Anna Karawajczyk James A. Bull Gessica Marchini Martyna Bielska Xenia Iwanowa Olga Bruno Paola Fossa Fabrizio Giordanetto 《Bioorganic & medicinal chemistry letters》2017,27(1):24-29
Phosphodiesterase 4 (PDE4) inhibitors have attractive therapeutic potential in respiratory, inflammatory, metabolic and CNS disorders. The present work details the design, chemical exploration and biological profile of a novel PDE4 inhibitor chemotype. A diazepinone ring was identified as an under-represented heterocyclic system fulfilling a set of PDE4 structure-based design hypotheses. Rapid exploration of the structure activity relationships for the series was enabled by robust and scalable two/three-steps parallel chemistry protocols. The resulting compounds demonstrated PDE4 inhibitory activity in cell free and cell-based assays comparable to the Zardaverine control used, suggesting potential avenues for their further development. 相似文献
903.
Yan Lou Francisco Lopez Yongying Jiang Xiaochun Han Chris Brotherton Roland Billedeau Steve Gabriel Shelly Gleason David M. Goldstein Ramona Hilgenkamp Buelent Kocer Lucja Orzechowski Jenny Tan Peter Wovkulich Bo Wen David Fry Paola Di Lello Lucy Chen Timothy D. Owens 《Bioorganic & medicinal chemistry letters》2017,27(3):632-635
Reactive metabolites have been putatively linked to many adverse drug reactions including idiosyncratic toxicities for a number of drugs with black box warnings or withdrawn from the market. Therefore, it is desirable to minimize the risk of reactive metabolite formation for lead molecules in optimization, in particular for non-life threatening chronic disease, to maximize benefit to risk ratio. This article describes our effort in addressing reactive metabolite issues for a series of 3-amino-2-pyridone inhibitors of BTK, e.g. compound 1 has a value of 459 pmol/mg protein in the microsomal covalent binding assay. Parallel approaches were taken to successfully resolve the issues: establishment of a predictive screening assay with correlation association of covalent binding assay, identification of the origin of reactive metabolite formation using MS/MS analysis of HLM as well as isolation and characterization of GSH adducts. This ultimately led to the discovery of compound 7 (RN941) with significantly reduced covalent binding of 26 pmol/mg protein. 相似文献
904.
905.
Marco Artini Paola Cicatiello Annarita Ricciardelli Rosanna Papa Laura Selan Principia Dardano 《Biofouling》2017,33(7):601-611
Staphylococcus epidermidis is a significant nosocomial pathogen in predisposed hosts because of its capability of forming a biofilm on indwelling medical devices. The initial stage of biofilm formation has a key role in S. epidermidis abiotic surface colonization. Recently, many strategies have been developed to create new anti-biofilm surfaces able to control bacterial adhesion mechanisms. In this work, the self-assembled amphiphilic layers formed by two fungal hydrophobins (Vmh2 and Pac3) have proven to be able to reduce the biofilm formed by different strains of S. epidermidis on polystyrene surfaces. The reduction in the biofilm thickness on the coated surfaces and the preservation of cell vitality have been demonstrated through confocal laser scanning microscope analysis. Moreover, the anti-biofilm efficiency of the self-assembled layers on different medically relevant materials has also been demonstrated using a CDC biofilm reactor. 相似文献
906.
Marino-Merlo Francesca Papaianni Emanuela Maugeri Teresa L. Zammuto Vincenzo Spanò Antonio Nicolaus Barbara Poli Annarita Di Donato Paola Mosca Claudia Mastino Antonio Gugliandolo Concetta 《Applied microbiology and biotechnology》2017,101(20):7487-7496
Applied Microbiology and Biotechnology - Herpes simplex virus type 1 (HSV-1) is responsible of common and widespread viral infections in humans through the world, and of rare, but extremely severe,... 相似文献
907.
908.
Increased Chondrogenic Potential of Mesenchymal Cells From Adipose Tissue Versus Bone Marrow‐Derived Cells in Osteoarthritic In Vitro Models
下载免费PDF全文
![点击此处可从《Journal of cellular physiology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
909.
IL‐10 expression in macrophages from neonates born from obese mothers is suppressed by IL‐4 and LPS/INFγ
下载免费PDF全文
![点击此处可从《Journal of cellular physiology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
910.