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排序方式: 共有508条查询结果,搜索用时 31 毫秒
1.
Viktoria M. S. Kjær Loukas Ieremias Dr. Viktorija Daugvilaite Dr. Michael Lückmann Prof. Thomas M. Frimurer Prof. Trond Ulven Prof. Mette M. Rosenkilde Dr. Jon Våbenø 《ChemMedChem》2021,16(17):2623-2627
The G protein-coupled receptor GPR183/EBI2, which is activated by oxysterols, is a therapeutic target for inflammatory and metabolic diseases where both antagonists and agonists are of potential interest. Using the piperazine diamide core of the known GPR183 antagonist (E)-3-(4-bromophenyl)-1-(4-(4-methoxybenzoyl)piperazin-1-yl)prop-2-en-1-one (NIBR189) as starting point, we identified and sourced 79 structurally related compounds that were commercially available. In vitro screening of this compound collection using a Ca2+ mobilization assay resulted in the identification of 10 compounds with agonist properties. To enable establishment of initial structure-activity relationship trends, these were supplemented with five in-house compounds, two of which were also shown to be GPR183 agonists. Taken together, our findings suggest that the agonist activity of this compound series is dictated by the substitution pattern of one of the two distal phenyl rings, which functions as a molecular efficacy-switch. 相似文献
2.
介绍探地雷达探测方法,探讨使用高频探地雷达探测粘土心墙堆石坝坝顶混凝土路面裂缝,达到快速、无损查明坝顶混凝土裂缝的性质与成因的目的. 相似文献
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Anna Laitakari Lingzhi Liu Thomas M. Frimurer Birgitte Holst 《International journal of molecular sciences》2021,22(8)
The G-protein coupled receptor GPR39 is abundantly expressed in various tissues and can be activated by changes in extracellular Zn2+ in physiological concentrations. Previously, genetically modified rodent models have been able to shed some light on the physiological functions of GPR39, and more recently the utilization of novel synthetic agonists has led to the unraveling of several new functions in the variety of tissues GPR39 is expressed. Indeed, GPR39 seems to be involved in many important metabolic and endocrine functions, but also to play a part in inflammation, cardiovascular diseases, saliva secretion, bone formation, male fertility, addictive and depression disorders and cancer. These new discoveries offer opportunities for the development of novel therapeutic approaches against many diseases where efficient therapeutics are still lacking. This review focuses on Zn2+ as an endogenous ligand as well as on the novel synthetic agonists of GPR39, placing special emphasis on the recently discovered physiological functions and discusses their pharmacological potential. 相似文献
5.
Alejandro Ordaz-Ramos Victor Hugo Rosales-Gallegos Jorge Melendez-Zajgla Vilma Maldonado Karla Vazquez-Santillan 《International journal of molecular sciences》2021,22(9)
Leucine-rich repeats containing G protein-coupled receptor 4 (LGR4) is a receptor that belongs to the superfamily of G protein-coupled receptors that can be activated by R-spondins (RSPOs), Norrin, circLGR4, and the ligand of the receptor activator of nuclear factor kappa-B (RANKL) ligands to regulate signaling pathways in normal and pathological processes. LGR4 is widely expressed in different tissues where it has multiple functions such as tissue development and maintenance. LGR4 mainly acts through the Wnt/β-catenin pathway to regulate proliferation, survival, and differentiation. In cancer, LGR4 participates in tumor progression, invasion, and metastasis. Furthermore, recent evidence reveals that LGR4 is essential for the regulation of the cancer stem cell population by controlling self-renewal and regulating stem cell properties. This review summarizes the function of LGR4 and its ligands in normal and malignant processes. 相似文献
6.
深圳市抛石填海区物探方法研究 总被引:2,自引:0,他引:2
在深圳某抛石填海区,由于存在较厚的淤泥层,而且在淤泥层中大量的分布着大小不均的石块,在物探作业的时候,往往难以探测到淤泥下面的基岩面,本文基于以上情况,通过对几种常规的物探方法的对比,从理论到实践,从中找到了最优的勘探方法,为以后从事此类工程的物探工作者提供一些借鉴。 相似文献
7.
前视探地雷达三维合成孔径成像及多视处理 总被引:1,自引:0,他引:1
提出了一种变波速条件下前视探地雷达三维合成孔径成像及多视处理方法。该方法利用非平稳卷积滤波处理在频率域重构目标图像频谱,经傅里叶反变换后实现前视探地雷达三维合成孔径成像;利用估计的目标入射角实现折射校正及前视探地雷达多视处理。对实测数据进行处理,结果证明了该方法的有效性。 相似文献
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岩溶地区水电站工程建设中对坝基岩体完整程度要求较高,为了探明坝基岩体中是否存在溶洞、溶隙和破碎带等不良地质体,应用地质雷达较准确地判断出了坝基下不良地质体的走向和规模,取得了良好的效果,为处理岩溶地质问题和工程安全施工提供了依据. 相似文献
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