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排序方式: 共有370条查询结果,搜索用时 31 毫秒
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Altun M Kramer HB Willems LI McDermott JL Leach CA Goldenberg SJ Kumar KG Konietzny R Fischer R Kogan E Mackeen MM McGouran J Khoronenkova SV Parsons JL Dianov GL Nicholson B Kessler BM 《Chemistry & biology》2011,18(11):1401-1412
Converting lead compounds into drug candidates is a crucial step in drug development, requiring early assessment of potency, selectivity, and off-target effects. We have utilized activity-based chemical proteomics to determine the potency and selectivity of deubiquitylating enzyme (DUB) inhibitors in cell culture models. Importantly, we characterized the small molecule PR-619 as a broad-range DUB inhibitor, and P22077 as a USP7 inhibitor with potential for further development as a chemotherapeutic agent in cancer therapy. A striking accumulation of polyubiquitylated proteins was observed after both selective and general inhibition of cellular DUB activity without direct impairment of proteasomal proteolysis. The repertoire of ubiquitylated substrates was analyzed by tandem mass spectrometry, identifying distinct subsets for general or specific inhibition of DUBs. This enabled identification of previously unknown functional links between USP7 and enzymes involved in DNA repair. 相似文献
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Forster J Rösner B Khusniyarov MM Streb C 《Chemical communications (Cambridge, England)》2011,47(11):3114-3116
A new mechanism for enhancing the visible light absorption of a homogeneous polyoxovanadate system is described. The photoactive pentanuclear {V(5)} isopolyoxovanadate cluster is formed in situ by a thermally-induced condensation reaction starting from a tetranuclear {V(4)} precursor. Upon irradiation with visible light, {V(5)} undergoes a light induced reduction reaction resulting in the formation of a 2-electron reduced {V(10)} cluster. Simultaneously, the oxidant methanol is selectively oxidized to formaldehyde. The {V(10)} cluster can subsequently be re-oxidized using H(2)O(2) or O(2). 相似文献
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Atkin R Borisenko N Drüschler M el-Abedin SZ Endres F Hayes R Huber B Roling B 《Physical chemistry chemical physics : PCCP》2011,13(15):6849-6857
The structure and dynamics of the interfacial layers between the extremely pure air- and water-stable ionic liquid 1-butyl-1-methylpyrrolidinium tris(pentafluoroethyl)trifluorophosphate and Au(111) has been investigated using in situ scanning tunneling microscopy, cyclic voltammetry, electrochemical impedance spectroscopy, and atomic force microscopy measurements. The in situ scanning tunnelling microscopy measurements reveal that the Au(111) surface undergoes a reconstruction, and at -1.2 V versus Pt quasi-reference the famous (22 × √3) herringbone superstructure is probed. Atomic force microscopy measurements show that multiple ion pair layers are present at the ionic liquid/Au interface which are dependent on the electrode potential. Upon applying cathodic electrode potentials, stronger ionic liquid near surface structure is detected: both the number of near surface layers and the force required to rupture these layers increases. The electrochemical impedance spectroscopy results reveal that three distinct processes take place at the interface. The fastest process is capacitive in its low-frequency limit and is identified with electrochemical double layer formation. The differential electrochemical double layer capacitance exhibits a local maximum at -0.2 V versus Pt quasi-reference, which is most likely caused by changes in the orientation of cations in the innermost layer. In the potential range between -0.84 V and -1.04 V, a second capacitive process is observed which is slower than electrochemical double layer formation. This process seems to be related to the herringbone reconstruction. In the frequency range below 1 Hz, the onset of an ultraslow faradaic process is found. This process becomes faster when the electrode potential is shifted to more negative potentials. 相似文献
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Heat production rates of chemical reactions or of biological cultures are a valuable signal, able to provide crucial information about the system under investigation. Commercially available bench-scale calorimeters reach a sensitivity of ≈100 mW/l. This sensitivity is usually sufficient for investigations in the field of reaction engineering or for safety studies. For the investigation of processes that exhibit only small exothermic or endothermic effects on the observation of the growth of biological material, the sensitivity of the calorimeter needs to be improved. This paper describes the modifications undertaken to reach a sensitivity of a few milliwatts per liter with an RC1 from Mettler-Toledo. 相似文献
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Rudolf Benedikt 《Fresenius' Journal of Analytical Chemistry》1892,31(1):563-565
Ohne Zusammenfassung 相似文献
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The experimental implications of neutral heavy leptons N in e+e? annihilation are examined. We calculate the production rate of both right-handed and left-handed N's at SPEAR and PEP/PETRA energies and show that observation of the process (or μ)π allows the determination of both the mass and handedness of N. 相似文献
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Ohne Zusammenfassung 相似文献