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排序方式: 共有3633条查询结果,搜索用时 15 毫秒
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Kun Liu Ravi Kurukulasuriya Kevin Dykstra Lisa DiMichelle Jinchu Liu Petr Vachal Anthony Ogawa Robert J. DeVita Dong-Ming Shen Qiang Tan Yili Chen Don Gauthier Andreas Verras Alejandro Crespo Beata Zamlynny Jeffrey Madwed Maarten Hoek Thomas Bateman Tim Cernak 《Bioorganic & medicinal chemistry letters》2019,29(14):1854-1858
The derivatization of pharmaceuticals is a core activity in the discovery and development of new medicines. Late-stage functionalization via modern CH functionalization chemistry has emerged as a powerful technique with which to diversify advanced pharmaceutical intermediates. We report herein a case study in late-stage functionalization towards the development of a new class of indazole-based mineralocorticoid receptor antagonists (MRA). An effort to modify the electronics of the core indazole heterocycle inspired the use of modern CH borylation chemistry. New reactivity patterns were revealed and studied computationally. Ultimately, a de novo synthesis delivered a key 6-fluoroindazole compound 26, a potent MRA with excellent metabolic stability. 相似文献
845.
Two recent papers outline improvements in gene editing technology that may facilitate the analysis of signaling networks important for development. The systems developed by both Thyagarajan and coworkers (Thyagarajan et al., 2007) in Nature Biotechnology, and Lombardo and colleagues (Lombardo et al., 2007) in Stem Cells, have the potential to advance our understanding of human embryonic stem cells. 相似文献
846.
Cowan C 《Developmental cell》2007,12(2):174-176
Polar body formation in eggs proceeds through two extreme asymmetric divisions, requiring precise coordination between spindle position and the polarized acto-myosin cortex. Two new studies appearing in this issue of Developmental Cell implicate the small GTPases Ran and Rac in cortical polarity of the mouse egg. 相似文献
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Looking for chinks in the armor of bacterial biofilms 总被引:1,自引:0,他引:1
Monroe D 《PLoS biology》2007,5(11):e307
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van Boven M Koopmans M Du Ry van Beest Holle M Meijer A Klinkenberg D Donnelly CA Heesterbeek HJ 《PLoS computational biology》2007,3(7):e145
Accumulating infections of highly pathogenic H5N1 avian influenza in humans underlines the need to track the ability of these viruses to spread among humans. A human-transmissible avian influenza virus is expected to cause clusters of infections in humans living in close contact. Therefore, epidemiological analysis of infection clusters in human households is of key importance. Infection clusters may arise from transmission events from (i) the animal reservoir, (ii) humans who were infected by animals (primary human-to-human transmission), or (iii) humans who were infected by humans (secondary human-to-human transmission). Here we propose a method of analysing household infection data to detect changes in the transmissibility of avian influenza viruses in humans at an early stage. The method is applied to an outbreak of H7N7 avian influenza virus in The Netherlands that was the cause of more than 30 human-to-human transmission events. The analyses indicate that secondary human-to-human transmission is plausible for the Dutch household infection data. Based on the estimates of the within-household transmission parameters, we evaluate the effectiveness of antiviral prophylaxis, and conclude that it is unlikely that all household infections can be prevented with current antiviral drugs. We discuss the applicability of our method for the detection of emerging human-to-human transmission of avian influenza viruses in particular, and for the analysis of within-household infection data in general. 相似文献