全文获取类型
收费全文 | 496篇 |
免费 | 15篇 |
国内免费 | 1篇 |
专业分类
512篇 |
出版年
2023年 | 4篇 |
2022年 | 9篇 |
2021年 | 15篇 |
2020年 | 15篇 |
2019年 | 13篇 |
2018年 | 12篇 |
2017年 | 8篇 |
2016年 | 25篇 |
2015年 | 19篇 |
2014年 | 18篇 |
2013年 | 36篇 |
2012年 | 40篇 |
2011年 | 44篇 |
2010年 | 11篇 |
2009年 | 17篇 |
2008年 | 32篇 |
2007年 | 34篇 |
2006年 | 32篇 |
2005年 | 31篇 |
2004年 | 25篇 |
2003年 | 31篇 |
2002年 | 13篇 |
2001年 | 8篇 |
2000年 | 4篇 |
1999年 | 5篇 |
1997年 | 1篇 |
1996年 | 1篇 |
1993年 | 1篇 |
1991年 | 1篇 |
1990年 | 1篇 |
1989年 | 2篇 |
1988年 | 2篇 |
1987年 | 1篇 |
1966年 | 1篇 |
排序方式: 共有512条查询结果,搜索用时 15 毫秒
101.
Zafer Sahin Merve Ertas Barkın Berk Sevde Nur Biltekin Leyla Yurttas Seref Demirayak 《Bioorganic & medicinal chemistry》2018,26(8):1986-1995
Steroidal and non-steroidal aromatase inhibitors target the suppression of estrogen biosynthesis in the treatment of breast cancer. Researchers have increasingly focused on developing non-steroidal derivatives for their potential clinical use avoiding steroidal side-effects.Non-steroidal derivatives generally have planar aromatic structures attached to the azole ring system. One part of this ring system comprises functional groups that inhibit aromatization through the coordination of the haem group of the aromatase enzyme. Replacement of the triazole ring system and development of aromatic/cyclic structures of the side chain can increase selectivity over aromatase enzyme inhibition.In this study, 4-(aryl/heteroaryl)-2-(pyrimidin-2-yl)thiazole derivatives were synthesized and physical analyses and structural determination studies were performed. The IC50 values were determined by a fluorescence-based aromatase inhibition assay and compound 1 (4-(2-hydroxyphenyl)-2-(pyrimidine-2-yl)thiazole) were found potent inhibitor of enzyme (IC50:0.42?nM). Then, their antiproliferative activity over MCF-7 and HEK-293 cell lines was evaluated using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Compounds 1, 7, 8, 13, 15, 18, 21 were active against MCF-7 breast cancer cells. Lastly, a series of docking experiments were undertaken to analyze the crystal structure of human placental aromatase and identify the possible interactions between the most active structure and the active site. 相似文献
102.
Priscilla F. McAuliffe Kurt W. Evans Argun Akcakanat Ken Chen Xiaofeng Zheng Hao Zhao Agda Karina Eterovic Takafumi Sangai Ashley M. Holder Chandeshwar Sharma Huiqin Chen Kim-Anh Do Emily Tarco Mihai Gagea Katherine A. Naff Aysegul Sahin Asha S. Multani Dalliah M. Black Elizabeth A. Mittendorf Isabelle Bedrosian Gordon B. Mills Ana Maria Gonzalez-Angulo Funda Meric-Bernstam 《PloS one》2016,11(3)
103.
104.
Alexandra M. Nicholson NiCole A. Finch Aleksandra Wojtas Matt C. Baker Ralph B. Perkerson III Monica Castanedes‐Casey Linda Rousseau Luisa Benussi Giuliano Binetti Roberta Ghidoni Ging‐Yuek R. Hsiung Ian R. Mackenzie Elizabeth Finger Bradley F. Boeve Nilüfer Ertekin‐Taner Neill R. Graff‐Radford Dennis W. Dickson Rosa Rademakers 《Journal of neurochemistry》2013,126(6):781-791
Frontotemporal lobar degeneration (FTLD) is the second leading cause of dementia in individuals under age 65. In many patients, the predominant pathology includes neuronal cytoplasmic or intranuclear inclusions of ubiquitinated TAR DNA binding protein 43 (FTLD‐TDP). Recently, a genome‐wide association study identified the first FTLD‐TDP genetic risk factor, in which variants in and around the TMEM106B gene (top SNP rs1990622) were significantly associated with FTLD‐TDP risk. Intriguingly, the most significant association was in FTLD‐TDP patients carrying progranulin (GRN) mutations. Here, we investigated to what extent the coding variant, rs3173615 (p.T185S) in linkage disequilibrium with rs1990622, affects progranulin protein (PGRN) biology and transmembrane protein 106 B (TMEM106B) regulation. First, we confirmed the association of TMEM106B variants with FTLD‐TDP in a new cohort of GRN mutation carriers. We next generated and characterized a TMEM106B‐specific antibody for investigation of this protein. Enzyme‐linked immunoassay analysis of progranulin protein levels showed similar effects upon T185 and S185 TMEM106B over‐expression. However, over‐expression of T185 consistently led to higher TMEM106B protein levels than S185. Cycloheximide treatment experiments revealed that S185 degrades faster than T185 TMEM106B, potentially due to differences in N‐glycosylation at residue N183. Together, our results provide a potential mechanism by which TMEM106B variants lead to differences in FTLD‐TDP risk.
105.
106.
Caglayan Berrak Kilic Ertugrul Dalay Arman Altunay Serdar Tuzcu Mehmet Erten Fusun Orhan Cemal Gunal Mehmet Yalcin Yulug Burak Juturu Vijaya Sahin Kazim 《Molecular biology reports》2019,46(1):241-250
Molecular Biology Reports - Traumatic brain injury (TBI) is the leading cause of mortality and morbidity in young adults and children in the industrialized countries; however, there are presently... 相似文献
107.
Loss of T cell CD98 H chain specifically ablates T cell clonal expansion and protects from autoimmunity 总被引:1,自引:0,他引:1
Cantor J Slepak M Ege N Chang JT Ginsberg MH 《Journal of immunology (Baltimore, Md. : 1950)》2011,187(2):851-860
CD98 H chain (4F2 Ag, Slc3a2) was discovered as a lymphocyte-activation Ag. Deletion of CD98 H chain in B cells leads to complete failure of B cell proliferation, plasma cell formation, and Ab secretion. In this study, we examined the role of T cell CD98 in cell-mediated immunity and autoimmune disease pathogenesis by specifically deleting it in murine T cells. Deletion of T cell CD98 prevented experimental autoimmune diabetes associated with dramatically reduced T cell clonal expansion. Nevertheless, initial T cell homing to pancreatic islets was unimpaired. In sharp contrast to B cells, CD98-null T cells showed only modestly impaired Ag-driven proliferation and nearly normal homeostatic proliferation. Furthermore, these cells were activated by Ag, leading to cytokine production (CD4) and efficient cytolytic killing of targets (CD8). The integrin-binding domain of CD98 was necessary and sufficient for full clonal expansion, pointing to a role for adhesive signaling in T cell proliferation and autoimmune disease. When we expanded CD98-null T cells in vitro, they adoptively transferred diabetes, establishing that impaired clonal expansion was responsible for protection from disease. Thus, the integrin-binding domain of CD98 is required for Ag-driven T cell clonal expansion in the pathogenesis of an autoimmune disease and may represent a useful therapeutic target. 相似文献
108.
Salih Saricaoglu Imen Nouioui Hilal Ay Hayrettin Saygin Kadriye Inan Bektas Kiymet Guven Demet Cetin Hans-Peter Klenk Kamil Isik Nevzat Sahin 《Antonie van Leeuwenhoek》2018,111(11):2051-2059
Strain H2R21T, a novel actinobacterium, isolated from a forest soil sample collected from Heybeliada, Istanbul, Turkey, and a polyphasic approach was used for characterisation of the strain. Chemotaxonomic and morphological characterisation of strain H2R21T indicated that it belongs to the genus Nonomuraea. 16S rRNA gene sequence similarity showed that the strain is closely related to Nonomuraea purpurea 1SM4-01T (99.1%) and Nonomuraea solani CGMCC 4.7037T (98.4%). DNA–DNA relatedness values were found to be lower than 70% between the isolate and its phylogenetic neighbours N. purpurea 1SM4-01T, N. solani CGMCC 4.7037T and Nonomuraea rhizophila YIM 67092T. The whole cell hydrolysates of strain H2R21T were found to contain meso-diaminopimelic acid as the diagnostic diamino acid and glucose, madurose, mannose and ribose as the cell sugars. The polar lipids were identified as phosphatidylglycerol, diphosphatidylglycerol, phosphatidylmethylethanolamine, phosphatidylethanolamine, hydroxy-phosphatidylethanolamine, dihydroxy-phosphatidylethanolamine, phosphatidylinositol, glycophosphatidylinositol, two glycophospholipids and two unidentified lipids. The predominant menaquinones were identified as MK-9(H4) and MK-9(H6). The major fatty acids were found to be iso-C16:0, iso-C16:0 2OH and C17:0 10-methyl. On the basis of DNA–DNA relatedness data and some phenotypic characteristics, it is evident that strain H2R21T can be distinguished from the closely related species in the genus Nonomuraea. Thus, it is concluded that strain H2R21T represents a novel species of the genus Nonomuraea, for which the name Nonomuraea insulae sp. nov. is proposed. The type strain is H2R21T (= DSM 102915T = CGMCC 4.7338T = KCTC 39769T). 相似文献
109.
110.
Alper Otunctemur Emin Ozbek Suleyman Sahin Levent Ozcan Murat Dursun Emre Can Polat Mustafa Cekmen Ozgur Doga Ozsoy Mustafa Erkoc Eyup Danis Muammer Bozkurt 《Andrologie》2016,26(1):1