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排序方式: 共有192条查询结果,搜索用时 15 毫秒
71.
Dr. Andreas Bergner Dr. Xiaoling Cockcroft Dr. Gerhard Fischer Dr. Andreas Gollner Wolfgang Hela Roland Kousek Dr. Andreas Mantoulidis Dr. Laetitia J. Martin Dr. Moriz Mayer Barbara Müllauer Gabriella Siszler Bernhard Wolkerstorfer Dr. Dirk Kessler Dr. Darryl B. McConnell 《Chemistry (Weinheim an der Bergstrasse, Germany)》2019,25(52):12037-12041
Natural products have proven to be a rich source of molecular architectures for drugs. Here, an integrated approach to natural product screening is proposed, which uncovered eight new natural product scaffolds for KRAS—the most frequently mutated oncogenic driver in human cancers, which has remained thus far undrugged. The approach combines aspects of virtual screening, fragment-based screening, structure-activity relationships (SAR) by NMR, and structure-based drug discovery to overcome the limitations in traditional natural product approaches. By using our approach, a new “snugness of fit” scoring function and the first crystal-soaking system of the active form of KRASG12D, the protein–ligand X-ray structures of a tricyclic indolopyrrole fungal alkaloid and an indoloisoquinolinone have been successfully elucidated. The natural product KRAS hits discovered provide fruitful ground for the optimization of highly potent natural-product-based inhibitors of the active form of oncogenic RAS. This integrated approach for screening natural products also holds promise for other “undruggable” targets. 相似文献
72.
73.
74.
75.
Additive-pulse mode locking of a diode-pumped Nd3+:YVO4 laser 总被引:2,自引:0,他引:2
We demonstrate self-starting additive-pulse mode locking of a diode-pumped Nd3+:YVO4 laser. Pulse durations of 2.7 ps are measured at a repetition frequency of 90.7 MHz and at an average output power of 1.1 W.
This corresponds to a peak power of 4.5 kW.
Received: 27 June 2001 / Revised version: 10 October 2001 / Published online: 29 November 2001 相似文献
76.
Interferon was originally described as an antiviral agent produced shortly after onset of infection with most viruses. However, in addition to inducing an antiviral state, interferon inhibits cell division, increases the expression of cell-surface antigens, boosts the cytotoxic activity of natural killer (NK) cells and modulates several immune functions of lymphocytes and macrophages. Moreover, a special class of interferon (immune interferon or IFN-gamma) is produced by T cells following stimulation with antigen or interaction with mitogens. The different methods by which interferon is induced and its multiple effects suggest that it may be part of a first-line defence system controlling the spread of virus infections and the proliferation of modified 'self' cells that have been affected by virus infection or neoplastic transformation. The ability of certain human lymphoma cells to activate the alternative pathway of complement is well established. Here we show that monoclonal antibody-purified interferon can amplify the ability of certain tumour cells to activate complement via the alternative pathway. This demonstration may reflect an additional, as yet unknown, role of interferon in inducing non-specific anti-tumour immunity. 相似文献
77.
78.
James McConnell 《Physica A》1980,102(3):539-546
Spectral densities of spherical harmonics arising from the rotational Brownian motion of molecules are calculated. The molecules are supposed to be spherical or linear, and account is taken of the influence of their inertia. When the results for a spherical molecule are applied to nuclear magnetic resonance, an expression for spin-lattice relaxation time is deduced and this is shown to provide a small correction to one calculated by Bloembergen, Purcell and Pound8). It is pointed out that the theory may be extended to nuclear magnetic processes when the thermal molecular motion is anisotropic. 相似文献
79.
Bose-Einstein condensation in a gas of sodium atoms 总被引:2,自引:0,他引:2
Davis KB Mewes M Andrews MR van Druten NJ Durfee DS Kurn DM Ketterle W 《Physical review letters》1995,75(22):3969-3973
80.
Kim D. Janda Wesley W. McConnell Gregory O. Nelson Michael E. Wright 《Journal of organometallic chemistry》1983,259(2):139-143
A new metal-metal bonded binuclear iron system [Me2SiCH2CH2SiMe2][η5-C5H4Fe(CO)2]2 (2) has been prepared by treating two equivalents of NaCp with one equivalent of ClSi(Me)2CH2CH2SiClMe2 obtaining the intermediate (C5H5)Si(Me)2CH2CH2Si(Me)2(C5H5) which then is directly allowed to react with Fe(CO)5 given 2 in 30% yield. From this cyclopentadienyldisilyl linked system three new binuclear irom complexes are formed. Treatment of 2 with Na/Hg in THF produced the dianion [Me2SiCH2CH2SiMe2][η5-C5H4Fe(CO)2?]2 which is quenched with CH3I giving [Me2SiCH2CH2SiMe2][η5-C4H4Fe(CO)2CH3]2 (4) in 76% yield. Complex 2 is oxidized with 1.2 equivalent of I2 to give [Me2SiCH2CH2SiMe2][η5-C5H4Fe(CO)2I]2 (5) in 85% yield. Photolysis of 5 (1 equiv.) and PPh3 (3 equiv.) results in the formation of the bis-substituted compound [Me2SiCH2CH2SiMe2][η5-C5H4Fe(CO)(PPh3)I]2 (6). These four new binuclear iron complexes are characterized by 1H, 13C, and 31P NMR and IR spectroscopy. 相似文献