全文获取类型
收费全文 | 201篇 |
免费 | 11篇 |
国内免费 | 11篇 |
专业分类
223篇 |
出版年
2024年 | 1篇 |
2023年 | 2篇 |
2022年 | 6篇 |
2021年 | 7篇 |
2020年 | 5篇 |
2019年 | 11篇 |
2018年 | 10篇 |
2017年 | 7篇 |
2016年 | 8篇 |
2015年 | 14篇 |
2014年 | 12篇 |
2013年 | 11篇 |
2012年 | 29篇 |
2011年 | 15篇 |
2010年 | 16篇 |
2009年 | 8篇 |
2008年 | 17篇 |
2007年 | 14篇 |
2006年 | 12篇 |
2005年 | 4篇 |
2004年 | 1篇 |
2003年 | 3篇 |
2002年 | 4篇 |
2001年 | 1篇 |
1998年 | 1篇 |
1996年 | 2篇 |
1994年 | 1篇 |
1991年 | 1篇 |
排序方式: 共有223条查询结果,搜索用时 0 毫秒
91.
APPL1 binds to adiponectin receptors and mediates adiponectin signalling and function 总被引:4,自引:0,他引:4
Mao X Kikani CK Riojas RA Langlais P Wang L Ramos FJ Fang Q Christ-Roberts CY Hong JY Kim RY Liu F Dong LQ 《Nature cell biology》2006,8(5):516-523
Adiponectin, also known as Acrp30, is an adipose tissue-derived hormone with anti-atherogenic, anti-diabetic and insulin sensitizing properties. Two seven-transmembrane domain-containing proteins, AdipoR1 and AdipoR2, have recently been identified as adiponectin receptors, yet signalling events downstream of these receptors remain poorly defined. By using the cytoplasmic domain of AdipoR1 as bait, we screened a yeast two-hybrid cDNA library derived from human fetal brain. This screening led to the identification of a phosphotyrosine binding domain and a pleckstrin homology domain-containing adaptor protein, APPL1 (adaptor protein containing pleckstrin homology domain, phosphotyrosine binding (PTB) domain and leucine zipper motif). APPL1 interacts with adiponectin receptors in mammalian cells and the interaction is stimulated by adiponectin. Overexpression of APPL1 increases, and suppression of APPL1 level reduces, adiponectin signalling and adiponectin-mediated downstream events (such as lipid oxidation, glucose uptake and the membrane translocation of glucose transport 4 (GLUT4)). Adiponectin stimulates the interaction between APPL1 and Rab5 (a small GTPase) interaction, leading to increased GLUT4 membrane translocation. APPL1 also acts as a critical regulator of the crosstalk between adiponectin signalling and insulin signalling pathways. These results demonstrate a key function for APPL1 in adiponectin signalling and provide a molecular mechanism for the insulin sensitizing function of adiponectin. 相似文献
92.
FtsY is the receptor of the signal recognition particle that mediates the targeting of integral membrane proteins in bacteria. It was shown that in Escherichia coli, the N-terminal region of FtsY contributes to its interaction with the membrane, but it is not inserted into the membrane. However, this study presents evidence that in Streptomyces coelicolor, FtsY has a hydrophobic region at its N-terminus, which forms a membrane insertion structure and contributes significantly to the binding between FtsY and membrane. Through membrane protein extraction followed by immunoblotting, we demonstrated that deletion of the N-terminal residues 11-39 from the S. coelicolor FtsY (ScFtsY) drastically reduced its membrane-binding capability and that the N-terminus of ScFtsY alone was capable of targeting the soluble EGFP protein onto the membrane with high efficiency. Furthermore, in a labeling experiment with the membrane-impermeable probe Mal-PEG, the ScFtsY N-terminal region was protected by the membrane and was not labeled. This observation indicates that this region was inserted into the membrane. 相似文献
93.
Jie Zhou Feibo Yu Bin Chen Xuming Wang Yong Yang Ye Cheng Chengqi Yan Jianping Chen 《Biotechnology letters》2013,35(7):1127-1133
Universal amiRNA vectors (pUAs) for constructing plant amiRNAs in Arabidopsis and rice have been developed. By using type IIg restriction enzyme, BaeI, a single amiRNA construct can be produced using only one PCR and one ligation reaction. Thus, only one pair of primers is required for each amiRNA vector and these can be designed to be compatible with existing or newly developed methods. Because the BaeI recognition sequence is completely digested, there is no modification to the miRNA backbone, therefore avoids the risk of sequence changes that may affect downstream analysis. Based on these vectors, specific amiRNA constructs were created and verified. With optimized parameters, 38–45 % colonies for each amiRNA construct contain insertions with the expected orientation, and approximately 80 % of these colonies have the correct sequences. 相似文献
94.
Coexpression Networks Implicate Human Midfetal Deep Cortical Projection Neurons in the Pathogenesis of Autism 总被引:1,自引:0,他引:1
A. Jeremy Willsey Stephan J. Sanders Mingfeng Li Shan Dong Andrew T. Tebbenkamp Rebecca A. Muhle Steven K. Reilly Leon Lin Sofia Fertuzinhos Jeremy A. Miller Michael T. Murtha Candace Bichsel Wei Niu Justin Cotney A. Gulhan Ercan-Sencicek Jake Gockley Abha R. Gupta Wenqi Han Xin He Ellen J. Hoffman Lambertus Klei Jing Lei Wenzhong Liu Li Liu Cong Lu Xuming Xu Ying Zhu Shrikant M. Mane Ed S. Lein Liping Wei James P. Noonan Kathryn Roeder Bernie Devlin Nenad Sestan Matthew W. State 《Cell》2013
95.
96.
97.
Pemphigus vulgaris (PV) is a potentially fatal blistering disease characterized by autoantibodies against the desmosomal adhesion protein desmoglein (Dsg) 3. Whether autoantibody steric hindrance or signaling through pathways such as p38 MAPK is primary in disease pathogenesis is controversial. PV mAbs that cause endocytosis of Dsg3 but do not dissociate keratinocytes because of compensatory adhesion by Dsg1 do not activate p38. The same mAbs plus exfoliative toxin to inactivate Dsg1 but not exfoliative toxin alone activate p38, suggesting that p38 activation is secondary to loss of adhesion. Mice with epidermal p38α deficiency blister after passive transfer of PV mAbs; however, acantholytic cells retain cell surface Dsg3 compared with wild-type mice. In cultured keratinocytes, p38 knockdown prevents loss of desmosomal Dsg3 by PV mAbs, and exogenous p38 activation causes internalization of Dsg3, desmocollin 3, and desmoplakin. p38α MAPK is therefore not required for the loss of intercellular adhesion in PV, but may function downstream to augment blistering via Dsg3 endocytosis. Treatments aimed at increasing keratinocyte adhesion could be used in conjunction with immunosuppressive agents, potentially leading to safer and more effective combination therapy regimens. 相似文献
98.
99.
100.