全文获取类型
收费全文 | 154篇 |
免费 | 6篇 |
出版年
2023年 | 2篇 |
2022年 | 1篇 |
2021年 | 2篇 |
2019年 | 1篇 |
2018年 | 1篇 |
2017年 | 1篇 |
2016年 | 4篇 |
2015年 | 5篇 |
2014年 | 5篇 |
2013年 | 9篇 |
2012年 | 14篇 |
2011年 | 13篇 |
2010年 | 5篇 |
2009年 | 4篇 |
2008年 | 7篇 |
2007年 | 9篇 |
2006年 | 9篇 |
2005年 | 6篇 |
2004年 | 10篇 |
2003年 | 7篇 |
2002年 | 8篇 |
2001年 | 5篇 |
2000年 | 1篇 |
1998年 | 1篇 |
1997年 | 1篇 |
1996年 | 1篇 |
1994年 | 3篇 |
1993年 | 4篇 |
1991年 | 2篇 |
1990年 | 3篇 |
1989年 | 3篇 |
1987年 | 2篇 |
1986年 | 8篇 |
1985年 | 1篇 |
1982年 | 1篇 |
1978年 | 1篇 |
排序方式: 共有160条查询结果,搜索用时 31 毫秒
61.
Pedarzani P McCutcheon JE Rogge G Jensen BS Christophersen P Hougaard C Strøbaek D Stocker M 《The Journal of biological chemistry》2005,280(50):41404-41411
SK channels are Ca2+-activated K+ channels that underlie after hyperpolarizing (AHP) currents and contribute to the shaping of the firing patterns and regulation of Ca2+ influx in a variety of neurons. The elucidation of SK channel function has recently benefited from the discovery of SK channel enhancers, the prototype of which is 1-EBIO. 1-EBIO exerts profound effects on neuronal excitability but displays a low potency and limited selectivity. This study reports the effects of DCEBIO, an intermediate conductance Ca2+-activated K+ channel modulator, and the effects of the recently identified potent SK channel enhancer NS309 on recombinant SK2 channels, neuronal apamin-sensitive AHP currents, and the excitability of CA1 neurons. NS309 and DCEBIO increased the amplitude and duration of the apamin-sensitive afterhyperpolarizing current without affecting the slow afterhyperpolarizing current in contrast to 1-EBIO. The potentiation by DCEBIO and NS309 was reversed by SK channel blockers. In current clamp experiments, NS309 enhanced the medium afterhyperpolarization (but not the slow afterhyperpolarization sAHP) and profoundly affected excitability by facilitating spike frequency adaptation in a frequency-independent manner. The potent and specific effect of NS309 on the excitability of CA1 pyramidal neurons makes this compound an ideal tool to assess the role of SK channels as possible targets for the treatment of disorders linked to neuronal hyperexcitability. 相似文献
62.
Strøbaek D Teuber L Jørgensen TD Ahring PK Kjaer K Hansen RS Olesen SP Christophersen P Skaaning-Jensen B 《Biochimica et biophysica acta》2004,1665(1-2):1-5
We have identified and characterized the compound NS309 (6,7-dichloro-1H-indole-2,3-dione 3-oxime) as a potent activator of human Ca2+ -activated K+ channels of SK and IK types, whereas it is devoid of effect on BK type channels. IK- and SK-channels have previously been reported to be activated by the benzimidazolinone, 1-EBIO and more potently by its dichloronated-analogue, DC-EBIO. NS309 is at least 1000 times more potent than 1-EBIO and at least 30 times more potent than DC-EBIO when the compounds are compared on the same cell. 相似文献
63.
Christian Thomsen Henrik Klitgaard Malcolm Sheardown† Helen C. Jackson Karen Eskesen† Palle Jacobsen‡ Svend Treppendahl§ Peter D. Suzdak 《Journal of neurochemistry》1994,62(6):2492-2495
Abstract: The in vivo anticonvulsant effects and in vitro metabo-tropic glutamate receptor selectivity of ( S )-4-carboxy-3-hydroxy-phenylglycine [(S)-4C3HPG] were examined. Intracerebroventricular injection of (S)-4C3HPG dose-dependently antagonized audiogenic-induced clonic and tonic convulsions in DBA/2 mice with ED60 values of 76 and 110-nmol per mouse, respectively. (S)-4C3HPG dose-dependently inhibited the spontaneously evoked epileptic spikes in a cingulate cortex-corpus callosum slice preparation. (SJ-4C3HPG displaced the binding of [3 H]glutamate in membranes prepared from baby hamster kidney (BHK) cells expressing the metabotropic glutamate receptor mGluR1a with an EC50 of 5 β 1 u M. ( S )-4C3HPG dose-dependently antagonized glutamate-stimulated phosphoinositide hydrolysis in BHK cells expressing mGluR 1a with an IC50 of 15 β 3 μ M. ( S )-4C3HPG was, however, an agonist at mGluR2 with an EC60 of 21 β 4 μ M for inhibition of forskolin-stimulated cyclic AMP formation in BHK cells expressing the mGluR2. ( S )-4C3HPG had no effects at mGluR4a. These data suggest that the anticonvulsant action of ( S )-4C3HPG is mediated by combined antagonism of mGluRIa and agonism of mGluR2. These results suggest the importance of mGluR1a and/or mGluR2 in the control of epileptic activity. 相似文献
64.
65.
66.
67.
Elzein E Kalla R Li X Perry T Parkhill E Palle V Varkhedkar V Gimbel A Zeng D Lustig D Leung K Zablocki J 《Bioorganic & medicinal chemistry letters》2006,16(2):302-306
A series of new 1,3-dipropyl-8-(1-heteroarylmethyl-1H-pyrazol-4-yl)-xanthine derivatives as A(2B)-AdoR antagonists have been synthesized and evaluated for their binding affinities for the A(2B), A(1), A(2A), and A(3)-AdoRs. 8-(1-((3-phenyl-1,2,4-oxadiazol-5-yl)methyl)-1H-pyrazol-4-yl)-1,3-dipropyl-1H-purine-2,6(3H,7H)-dione (4) displayed high affinity (K(i)=1 nM) and selectivity for the A(2B)-AdoR versus A(1), A(2A), and A(3)-AdoRs (A(1)/A(2B), A(2A)/A(2B), and A(3)/A(2B) selectivity ratios of 370, 1100, and 480, respectively). The synthesis and SAR of this novel class of compounds are presented herein. 相似文献
68.
69.
Ihn Young Song Komaraiah Palle Aditi Gurkar Satoshi Tateishi Gary M. Kupfer Cyrus Vaziri 《The Journal of biological chemistry》2010,285(41):31525-31536
Fanconi anemia (FA) is a cancer susceptibility syndrome characterized by sensitivity to DNA-damaging agents. The FA proteins (FANCs) are implicated in DNA repair, although the precise mechanisms by which FANCs process DNA lesions are not fully understood. An epistatic relationship between the FA pathway and translesion synthesis (TLS, a post-replication DNA repair mechanism) has been suggested, but the basis for cross-talk between the FA and TLS pathways is poorly understood. We show here that ectopic overexpression of the E3 ubiquitin ligase Rad18 (a central regulator of TLS) induces DNA damage-independent mono-ubiquitination of proliferating cell nuclear antigen (PCNA) (a known Rad18 substrate) and FANCD2. Conversely, DNA damage-induced mono-ubiquitination of both PCNA and FANCD2 is attenuated in Rad18-deficient cells, demonstrating that Rad18 contributes to activation of the FA pathway. WT Rad18 but not an E3 ubiquitin ligase-deficient Rad18 C28F mutant fully complements both PCNA ubiquitination and FANCD2 activation in Rad18-depleted cells. Rad18-induced mono-ubiquitination of FANCD2 is not observed in FA core complex-deficient cells, demonstrating that Rad18 E3 ligase activity alone is insufficient for FANCD2 ubiquitylation. Instead, Rad18 promotes FA core complex-dependent FANCD2 ubiquitination in a manner that is secondary to PCNA mono-ubiquitination. Taken together, these results demonstrate a novel Rad18-dependent mechanism that couples activation of the FA pathway with TLS. 相似文献
70.
Synthesis and biological activity of N-substituted aminocarbonyl-1,3-dioxolanes as VLA-4 antagonists
Abdul Rehman Ajay Soni Keshav Naik Sreeji Nair Venkata P. Palle Sunanda Dastidar Abhijit Ray M.S. Alam Mohammad Salman Ian A. Cliffe Viswajanani Sattigeri 《Bioorganic & medicinal chemistry letters》2010,20(18):5514-5520
A novel set of compounds with a 1,3-dioxolane ring which acts as a proline bioisostere have been successfully designed as VLA-4 receptor antagonists. Compounds (18e), (28j), and (35g) were shown to have high receptor affinities. 相似文献