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排序方式: 共有8865条查询结果,搜索用时 15 毫秒
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Birong Zhang James R. Kiefer Robert A. Blake Jae H. Chang Steven Hartman Ellen Rei Ingalla Tracy Kleinheinz Vidhi Mody Michelle Nannini Daniel F. Ortwine Yingqing Ran Amy Sambrone Deepak Sampath Maia Vinogradova Yu Zhong Jerome C. Nwachukwu Kendall W. Nettles Tommy Lai Jun Liang 《Bioorganic & medicinal chemistry letters》2019,29(7):905-911
Despite tremendous progress made in the understanding of the ERα signaling pathway and the approval of many therapeutic agents, ER+?breast cancer continues to be a leading cause of cancer death in women. We set out to discover compounds with a dual mechanism of action in which they not only compete with estradiol for binding with ERα, but also can induce the degradation of the ERα protein itself. We were attracted to the constrained chromenes containing a tetracyclic benzopyranobenzoxepine scaffold, which were reported as potent selective estrogen receptor modulators (SERMs). Incorporation of a fluoromethyl azetidine side chain yielded highly potent and efficacious selective estrogen receptor degraders (SERDs), such as 16aa and surprisingly, also its enantiomeric pair 16ab. Co-crystal structures of the enantiomeric pair 16aa and 16ab in complex with ERα revealed default (mimics the A-D rings of endogenous ligand estradiol) and core-flipped binding modes, rationalizing the equivalent potency observed for these enantiomers in the ERα degradation and MCF-7 anti-proliferation assays. 相似文献
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Houcong Wang Huakang Huang Simi Qiu Shi Zhang Yashun Fang Jinlei Cai Xuan Zheng Yumin Huang Ruming Chen Chuanzhi Sun Shuanglong Chen Xiaowen Chi Xinying Liao Weiqing Zhang Xinbin Zhong 《生物学前沿》2007,2(2):144-150
After 20 years of dedicated research,Jiafuzhan has been successfully developed under the new technologies in breeding high-quality early indica rice cultivars.Its rice quality has almost reached the A-level Editable Rice of Agriculture Department of China,and its average production reaches 400-500 kg/(666.7 m2).This new cultivar also has other characteristics such as enhanced resistance of blast and fallen,steady productivity,and strong adaptability.Jiafuzhan has been put into production of over 11.4×104 hm2 in Fujian Province and has been introduced and extended in other Provinces like Jiangxi,Guangdong,and Guangxi,China.The successes of breeding Jiafuzhan is a solution to the existing perennial problems in the rice industry,such as poor grain quality of big-grain rice and early indica rice,low productivity,and poor blast resistance of elite rice. 相似文献
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Plant and Soil - Iron plaque at the soil-root interface is a key position for uptake of heavy metals by plants. Exploring iron plaque’s role in Pb uptake by edible vegetable roots aids... 相似文献
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Kai‐Wei Yu Ning Zhong Yu Xiao Zhen‐Yu She 《Biology of the cell / under the auspices of the European Cell Biology Organization》2019,111(6):143-160
Chromosome congression is essential for faithful chromosome segregation and genomic stability in cell division. Centromere‐associated protein E (CENP‐E), a plus‐end‐directed kinesin motor, is required for congression of pole‐proximal chromosomes in metaphase. CENP‐E accumulates at the outer plate of kinetochores and mediates the kinetochore‐microtubule capture. CENP‐E also transports the chromosomes along spindle microtubules towards the equatorial plate. CENP‐E interacts with Bub1‐related kinase, Aurora B and core kinetochore components during kinetochore–microtubule attachment. In this review, we introduce the structures and mechanochemistry of kinesin‐7 CENP‐E. We highlight the complicated interactions between CENP‐E and partner proteins during chromosome congression. We summarise the detailed roles and mechanisms of CENP‐E in mitosis and meiosis, including the kinetochore–microtubule capture, chromosome congression/alignment in metaphase and the regulation of spindle assembly checkpoint. We also shed a light on the roles of CENP‐E in tumourigenesis and CENP‐E's specific inhibitors. 相似文献
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Long Huiping Zhong Gang Wang Chengzhi Zhang Jian Zhang Yueling Luo Jinglian Shi Shengliang 《Neurochemical research》2019,44(8):1830-1839
Neurochemical Research - The pathogenesis of late-onset Alzheimer's disease (LOAD) mainly involves abnormal accumulation of extracellular β-amyloid (Aβ) and the consequent neurotoxic... 相似文献
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