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排序方式: 共有137条查询结果,搜索用时 672 毫秒
31.
32.
Elena Galfrè Lauretta Galeno Oscar Moran 《Cellular and molecular life sciences : CMLS》2012,69(21):3701-3713
Nucleotide binding domains (NBD1 and NBD2) of the cystic fibrosis transmembrane conductance regulator (CFTR), the defective protein in cystic fibrosis, are responsible for controlling the gating of the chloride channel and are the putative binding sites for several candidate drugs in the disease treatment. We studied the effects of the application of 2-pyrimidin-7,8-benzoflavone (PBF), a strong potentiator of the CFTR, on the properties of recombinant and equimolar NBD1/NBD2 mixture in solution. The results indicate that the potentiator induces significant conformational changes of the NBD1/NBD2 dimer in solution. The potentiator does not modify the ATP binding constant, but reduces the ATP hydrolysis activity of the NBD1/NBD2 mixture. The intrinsic fluorescence and the guanidinium denaturation measurements indicate that the potentiator induces different conformational changes on the NBD1/NBD2 mixture in the presence and absence of ATP. It was confirmed from small-angle X-ray scattering experiments that, in absence of ATP, the NBD1/NBD2 dimer was disrupted by the potentiator, but in the presence of 2?mM ATP, the two NBDs kept dimerised, and a major change in the size and the shape of the structure was observed. We propose that these conformational changes could modify the NBDs–intracellular loop interaction in a way that would facilitate the open state of the channel. 相似文献
33.
Francesca Cherubino Andreea Miszner Maria Daniela Renna Rachele Sangaletti Stefano Giovannardi Elena Bossi 《Cellular and molecular life sciences : CMLS》2009,66(23):3797-3808
The effects of three tricyclic antidepressants (TCAs) and two serotonin selective reuptake inhibitors (SSRIs) have been studied
with an electrophysiological approach on Xenopus laevis oocytes expressing the rat GABA (γ-Aminobutyric-acid) transporter rGAT1. All tested TCAs and SSRIs inhibit the GABA-associated
current in a dose-dependent way with low but comparable efficacy. The pre-steady-state and uncoupled currents appear substantially
unaffected. The efficacy of desipramine, but not of the other drugs, is strongly increased in the lysine-glutamate or -aspartate
mutants K448E and K448D. Comparison of I
max and K
0.5GABA in the absence and presence of desipramine showed that both parameters are reduced by the drug in the wild-type and in the
K448E mutant. This suggests an uncompetitive inhibition, in which the drug can bind only after the substrate, an explanation
in agreement with the lack of effects on the pre-steady-state and leak currents, and with the known structural data. 相似文献
34.
Zhu P Liu J Bess J Chertova E Lifson JD Grisé H Ofek GA Taylor KA Roux KH 《Nature》2006,441(7095):847-852
Envelope glycoprotein (Env) spikes on AIDS retroviruses initiate infection of host cells and are therefore targets for vaccine development. Though crystal structures for partial Env subunits are known, the structure and distribution of native Env spikes on virions is obscure. We applied cryoelectron microscopy tomography to define ultrastructural details of spikes. Virions of wild-type human immunodeficiency virus 1 (HIV-1) and a mutant simian immunodeficiency virus (SIV) had approximately 14 and approximately 73 spikes per particle, respectively, with some clustering of HIV-1 spikes. Three-dimensional averaging showed that the surface glycoprotein (gp120) 'head' of each subunit of the trimeric SIV spike contains a primary mass, with two secondary lobes. The transmembrane glycoprotein 'stalk' of each trimer is composed of three independent legs that project obliquely from the trimer head, tripod-like. Reconciling available atomic structures with the three-dimensional whole spike density map yields insights into the orientation of Env spike structural elements and possible structural bases of their functions. 相似文献
35.
Mazzali PA Deng J Nomoto K Sauer DN Pian E Tominaga N Tanaka M Maeda K Filippenko AV 《Nature》2006,442(7106):1018-1020
Supernovae connected with long-duration gamma-ray bursts (GRBs) are hyper-energetic explosions resulting from the collapse of very massive stars ( approximately 40 M\circ, where M\circ is the mass of the Sun) stripped of their outer hydrogen and helium envelopes. A very massive progenitor, collapsing to a black hole, was thought to be a requirement for the launch of a GRB. Here we report the results of modelling the spectra and light curve of SN 2006aj (ref. 9), which demonstrate that the supernova had a much smaller explosion energy and ejected much less mass than the other GRB-supernovae, suggesting that it was produced by a star whose initial mass was only approximately 20 M\circ. A star of this mass is expected to form a neutron star rather than a black hole when its core collapses. The smaller explosion energy of SN 2006aj is matched by the weakness and softness of GRB 060218 (an X-ray flash), and the weakness of the radio flux of the supernova. Our results indicate that the supernova-GRB connection extends to a much broader range of stellar masses than previously thought, possibly involving different physical mechanisms: a 'collapsar' (ref. 8) for the more massive stars collapsing to a black hole, and magnetic activity of the nascent neutron star for the less massive stars. 相似文献
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37.
Yu W Ginjala V Pant V Chernukhin I Whitehead J Docquier F Farrar D Tavoosidana G Mukhopadhyay R Kanduri C Oshimura M Feinberg AP Lobanenkov V Klenova E Ohlsson R 《Nature genetics》2004,36(10):1105-1110
Chromatin insulators demarcate expression domains by blocking the cis effects of enhancers or silencers in a position-dependent manner. We show that the chromatin insulator protein CTCF carries a post-translational modification: poly(ADP-ribosyl)ation. Chromatin immunoprecipitation analysis showed that a poly(ADP-ribosyl)ation mark, which exclusively segregates with the maternal allele of the insulator domain in the H19 imprinting control region, requires the bases that are essential for interaction with CTCF. Chromatin immunoprecipitation-on-chip analysis documented that the link between CTCF and poly(ADP-ribosyl)ation extended to more than 140 mouse CTCF target sites. An insulator trap assay showed that the insulator function of most of these CTCF target sites is sensitive to 3-aminobenzamide, an inhibitor of poly(ADP-ribose) polymerase activity. We suggest that poly(ADP-ribosyl)ation imparts chromatin insulator properties to CTCF at both imprinted and nonimprinted loci, which has implications for the regulation of expression domains and their demise in pathological lesions. 相似文献
38.
A new, tenth subunit of TFIIH is responsible for the DNA repair syndrome trichothiodystrophy group A 总被引:21,自引:0,他引:21
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40.