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排序方式: 共有130条查询结果,搜索用时 15 毫秒
21.
Lan-Ying Qin Zheming Ruan Robert J. Cherney T.G. Murali Dhar James Neels Carolyn A. Weigelt John S. Sack Anurag S. Srivastava Lyndon A.M. Cornelius Joseph A. Tino Kevin Stefanski Xiaomei Gu Jenny Xie Vojkan Susulic Xiaoxia Yang Melissa Yarde-Chinn Stacey Skala Ruth Bosnius Michael A. Poss 《Bioorganic & medicinal chemistry letters》2017,27(4):855-861
As demonstrated in preclinical animal models, the disruption of PI3Kδ expression or its activity leads to a decrease in inflammatory and immune responses. Therefore, inhibition of PI3Kδ may provide an alternative treatment for autoimmune diseases, such as RA, SLE, and respiratory ailments. Herein, we disclose the identification of 7-(3-(piperazin-1-yl)phenyl)pyrrolo[2,1-f][1,2,4]triazin-4-amine derivatives as highly potent, selective and orally bioavailable PI3Kδ inhibitors. The lead compound demonstrated efficacy in an in vivo mouse KLH model. 相似文献
22.
Purandare AV Chen Z Huynh T Pang S Geng J Vaccaro W Poss MA Oconnell J Nowak K Jayaraman L 《Bioorganic & medicinal chemistry letters》2008,18(15):4438-4441
This study reports the identification and Hits to Leads optimization of inhibitors of coactivator associated arginine methyltransferase (CARM1). Compound 7b is a potent, selective inhibitor of CARM1. 相似文献
23.
Gentles RG Hu S Huang Y Grant-Young K Poss MA Andres C Fiedler T Knox R Lodge N Weaver CD Harden DG 《Bioorganic & medicinal chemistry letters》2008,18(20):5694-5697
An exploratory SAR study on a series of potent, non-apamin-displacing 4-(aminomethylaryl)pyrazolopyrimidine K(Ca) channel blockers is described and their selectivity against K(Ca) channel subtypes is reported. The most potent analog, 5-chloro-N-(thiophen-2-ylmethyl)pyrazolo[1,5-a]pyrimidin-7-amine (24) displayed sub-micromolar activity in both a thallium flux and whole-cell electrophysiology assay and did not displace apamin in a competitive binding study. 相似文献
24.
This study reports two novel selective differential media. A first differential medium can be applied in methods for the isolation of non-O157 Shiga toxin-producing Escherichia coli (STEC) serotypes (O26, O103, O111 and O145) from food or faeces. A second differential medium was designed for both sorbitol-positive and -negative O157 STEC strains. Selective differential media are based on a chromogenic compound to signal beta-galactosidase activity and one or more fermentative carbon sources. The chromogenic marker and carbohydrates were combined with a pH indicator and several inhibitory components, which resulted in highly specific differentiation media. Consecutive use of a serotype-dependent choice of confirmation media resulted in a very low incidence of false-positive isolates when comparing clinical STEC strains with a collection of commensal E. coli strains. 相似文献
25.
Tram Huynh Zhong Chen Suhong Pang Jieping Geng Tiziano Bandiera Simona Bindi Paola Vianello Fulvia Roletto Sandrine Thieffine Arturo Galvani Wayne Vaccaro Michael A. Poss George L. Trainor Matthew V. Lorenzi Marco Gottardis Lata Jayaraman Ashok V. Purandare 《Bioorganic & medicinal chemistry letters》2009,19(11):2924-2927
Design, synthesis, and SAR development led to the identification of the potent, novel, and selective pyrazole based inhibitor (7f) of Coactivator Associated Arginine Methyltransferase (CARM1). 相似文献
26.
Tasir S. Haque Ningning Liang Rajasree Golla Ramakrishna Seethala Zhengping Ma William R. Ewing Christopher B. Cooper Mary Ann Pelleymounter Michael A. Poss Dong Cheng 《Bioorganic & medicinal chemistry letters》2009,19(20):5872-5876
We report the synthesis and enzymatic evaluation of potent inhibitors of acetyl-CoA carboxylases (ACCs) containing biphenyl or 3-phenyl pyridine cores. These compounds inhibit both ACC1 and ACC2, or are moderately selective for either enzyme, depending on side chain substitution. Typical activities of the most potent compounds in this class are in the low double-digit to single-digit nanomolar range in in vitro assays using human ACC1 and ACC2 enzymes. 相似文献
27.
Purandare AV Wan H Gao A Somerville J Burke C Vaccaro W Yang X McIntyre KW Poss MA 《Bioorganic & medicinal chemistry letters》2006,16(1):204-207
The design, synthesis, and activity of novel and selective small molecule antagonists of the CC chemokine receptor-4 (CCR4) are presented. Compound 8c was efficacious in a murine allergic inflammation model (ED(50) 30 mg/kg). 相似文献
28.
29.
Roles for Fgf signaling during zebrafish fin regeneration 总被引:7,自引:0,他引:7
Poss KD Shen J Nechiporuk A McMahon G Thisse B Thisse C Keating MT 《Developmental biology》2000,222(2):347-358
30.
Chen-Hui Chen Alexander F. Merriman Jeremiah Savage Jason Willer Taylor Wahlig Nicholas Katsanis Viravuth P. Yin Kenneth D. Poss 《PLoS genetics》2015,11(8)
The first critical stage in salamander or teleost appendage regeneration is creation of a specialized epidermis that instructs growth from underlying stump tissue. Here, we performed a forward genetic screen for mutations that impair this process in amputated zebrafish fins. Positional cloning and complementation assays identified a temperature-sensitive allele of the ECM component laminin beta 1a (lamb1a) that blocks fin regeneration. lamb1a, but not its paralog lamb1b, is sharply induced in a subset of epithelial cells after fin amputation, where it is required to establish and maintain a polarized basal epithelial cell layer. These events facilitate expression of the morphogenetic factors shha and lef1, basolateral positioning of phosphorylated Igf1r, patterning of new osteoblasts, and regeneration of bone. By contrast, lamb1a function is dispensable for juvenile body growth, homeostatic adult tissue maintenance, repair of split fins, or renewal of genetically ablated osteoblasts. fgf20a mutations or transgenic Fgf receptor inhibition disrupt lamb1a expression, linking a central growth factor to epithelial maturation during regeneration. Our findings reveal transient induction of lamb1a in epithelial cells as a key, growth factor-guided step in formation of a signaling-competent regeneration epidermis. 相似文献