全文获取类型
收费全文 | 72篇 |
免费 | 3篇 |
专业分类
化学 | 36篇 |
数学 | 11篇 |
物理学 | 28篇 |
出版年
2021年 | 1篇 |
2016年 | 4篇 |
2015年 | 1篇 |
2014年 | 2篇 |
2013年 | 3篇 |
2012年 | 3篇 |
2011年 | 4篇 |
2010年 | 3篇 |
2009年 | 1篇 |
2008年 | 3篇 |
2007年 | 4篇 |
2006年 | 4篇 |
2005年 | 3篇 |
2004年 | 7篇 |
2003年 | 3篇 |
2002年 | 3篇 |
2000年 | 1篇 |
1999年 | 1篇 |
1997年 | 1篇 |
1996年 | 1篇 |
1994年 | 2篇 |
1993年 | 3篇 |
1992年 | 3篇 |
1991年 | 1篇 |
1990年 | 1篇 |
1989年 | 1篇 |
1984年 | 1篇 |
1983年 | 2篇 |
1982年 | 1篇 |
1978年 | 1篇 |
1977年 | 2篇 |
1976年 | 1篇 |
1975年 | 1篇 |
1916年 | 1篇 |
1903年 | 1篇 |
排序方式: 共有75条查询结果,搜索用时 15 毫秒
51.
Synthesis and pharmacology of glutamate receptor ligands: new isothiazole analogues of ibotenic acid
Jørgensen CG Clausen RP Hansen KB Bräuner-Osborne H Nielsen B Metzler B Metzler BB Kehler J Krogsgaard-Larsen P Madsen U 《Organic & biomolecular chemistry》2007,5(3):463-471
The naturally occurring heterocyclic amino acid ibotenic acid (Ibo) and the synthetic analogue thioibotenic acid (Thio-Ibo) possess interesting but dissimilar pharmacological activity at ionotropic and metabotropic glutamate receptors (iGluRs and mGluRs). Therefore, a series of Thio-Ibo analogues was synthesized. The synthesis included introduction of substituents by Suzuki and Grignard reactions on 4-halogenated 3-benzyloxyisothiazolols, reduction of the obtained alcohols, followed by introduction of the amino acid moiety by use of 2-(N-tert-butoxycarbonylimino)malonic acid diethyl ester. The obtained Thio-Ibo analogues (1, 2a-g) were characterized in functional assays on recombinant mGluRs and in receptor binding assays on native iGluRs. At mGluRs, the activity at Group II was retained for compounds with small substituents (2a-2d), whereas the Group I and Group III receptor activities for all new compounds were lost. Detection of NMDA receptor affinity prompted further characterization, and two-electrode voltage-clamp recordings at recombinant NMDA receptor subtypes NR1/NR2A-D expressed in Xenopus oocytes were carried out for compounds with small substituents (chloro, bromo, methyl or ethyl, compounds 2a-d). This series of Thio-Ibo analogues defines a structural threshold for NMDA receptor activation and reveals that the individual subtypes have different steric requirements for receptor activation. The compounds 2a and 2c are the first examples of agonists discriminating individual NMDA subtypes. 相似文献
52.
Kaae BH Harpsøe K Kastrup JS Sanz AC Pickering DS Metzler B Clausen RP Gajhede M Sauerberg P Liljefors T Madsen U 《Chemistry & biology》2007,14(11):1294-1303
Dimeric positive allosteric modulators of ionotropic glutamate receptors were designed, synthesized, and characterized pharmacologically in electrophysiological experiments. The designed compounds are dimers of arylpropylsulfonamides and have been constructed without a linker. The monomeric arylpropylsulfonamides were derived from known modulators and target the cyclothiazide-binding site at the AMPA receptors. The three stereoisomers--R,R, meso, and S,S--of the two constructed dimers were prepared, and in vitro testing showed the R,R forms to be the most potent stereoisomers. The biarylpropylsulfonamides have dramatically increased potencies, more than three orders of magnitude higher than the corresponding monomers. Dimer (R,R)-2a was cocrystallized with the GluR2-S1S2J construct, and an X-ray crystallographic analysis showed (R,R)-2a to bridge two identical binding pockets on two neighboring GluR2 subunits. Thus, this is biostructural evidence of a homomeric dimer bridging two identical receptor-binding sites. 相似文献
53.
Birgitte Georg Lene Rask Jens Hannibal Jan Fahrenkrug 《Photochemistry and photobiology》2014,90(5):1069-1076
We established a cell line (HEK‐hMel) expressing melanopsin in a tetracycline dependent manner to elucidate new aspects of melanopsin's light response. Different light stimuli were evaluated using FOS expression as response parameter. Immunoblotting was used to evaluate expression of melanopsin and FOS and qPCR to quantify FOS mRNA responses. The magnitude of the FOS response was found to correlate with the amount of melanopsin expressed by the cells, and a transient FOS mRNA induction followed by FOS protein still elevated after 24 h of illumination was revealed. Exposing the cells to darkness after light resulted in reduction of the response compared to exposure to light solely showing dependency on continuous light. Increasing irradiances of blue light (480 nm) up to 1011 quanta cm?2 s?1 elicited steep increases in FOS mRNA, while increases between 1012 and 5 × 1013 quanta cm?2 s?1 resulted in equally high FOS expression. The HEK‐hMel cells were used to characterize facets of melanopsin's light‐induced FOS response not approachable in vivo. Novel information such as dependency of the FOS response on both melanopsin amount and light intensity in addition to a detailed time‐course of both FOS mRNA and protein were revealed. 相似文献
54.
55.
The structural and electronic properties of the intermixed interfaces of layered Au/Te/n-GaAs structures were investigated by the combined application of129I Mössbauer spectroscopy (in the decay of129mTe), X-ray diffraction, Raman spectroscopy and electrical measurements. The transition from Schottky-type to ohmic contact by high fluence pulsed laser irradiation was examined and compared to rapid time furnace heat treatment. Distinctly different ohmic contact formation mechanisms have been observed. Whereas for furnace alloying the formation of a crystalline (graded As doped) Ga2Te3 interface layer is crucial, strong evidence is adduced that the ohmic character of high-fluence laser mixed structures is correlated to the formation of a high density of defect complexes in the GaAs top layer. 相似文献
56.
Floris L. Wuyts Louis Heylen Fons Mertens Marc De Bodt Paul H. Van de Heyning 《Journal of voice》2002,16(4):460-465
Normative voice range profiles (VRPs) are calculated for a group of untrained boys and girls between 6 and 11 years based on 35 and 39 recordings, respectively. All individuals had healthy voices. These normative VRPs contain 95% prediction intervals (PI) for both frequency and intensity. They are based on a series of mathematical transformations of the original individual VRPs in order to maintain in the normative VRPs the typical oval VRP shape including the dip between modal and falsetto register. The presented normative VRPs are directly applicable in the clinical practice of otolaryngologists and speech-language pathologists. 相似文献
57.
We show that there exists a natural approach version of the topological Vietoris hyperspace construction [16], [17] which has several advantages over the topological version. In the first place the important structural fact that the Vietoris construction can now also be considered, not only for topological but also intrinsically for metric spaces, but equally important in the second place the fact that we can considerably strengthen fundamental classic results. In this paper we mainly pay attention to properties concerning or involving compactness. As main results, in the first place we prove that it is not merely compactness of the Vietoris hyperspace which is equivalent to compactness of the original space [3] but that actually in the approach setting the indices of compactness [7], [8], [9], [10] numerically completely coincide. In the second place the well-known result [3], [4], [15] which says that if the original space is compact metric then the Vietoris topology is metrizable by the Hausdorff metric gets strengthened in the sense that in the approach setting under the same conditions the Vietoris approach structure actually coincides with the Hausdorff metric. Classic results follow as easy corollaries. Besides these main results we also draw attention to the good functorial relationship between the Vietoris approach structures and the associated topologies. 相似文献
58.
Regenberg B Krühne U Beyer M Pedersen LH Simon M Thomas OR Nielsen J Ahl T 《Lab on a chip》2004,4(6):654-657
Laminar flow in microfluidic chambers was used to construct low (one dimensional) density arrays suitable for miniaturized biochemical assays. By varying the ratio of flows of two guiding streams flanking a sample stream, precise focusing and positioning of the latter was achieved, and reactive species carried in the sample stream were deposited on functionalized chip surfaces as discrete 50 microm wide lanes. Using different model systems we have confirmed the method's suitability for qualitative screening and quantification tasks in receptor-ligand assays, recording biotin-streptavidin interactions, DNA-hybridization and DNA-triplex formation. The system is simple, fast, reproducible, flexible, and has small sample requirements. 相似文献
59.
The experimental results of self-injection locking of an antireflection-coated broad-area diode laser with a 1000-microm-wide emitting area are presented. To our knowledge, it is the broadest single-element diode laser that has been used in an external-feedback cavity until now. Usually, wide diode lasers suffer from filamentation, which leads to poor spatial beam quality. We show, however, that the beam quality of the diode laser is improved significantly when we use asymmetric self-injection locking. An output power of 2.05 W is obtained with a beam quality factor M2 of 2.7. The self-injection locking technique improves the beam quality by a factor of 107. By comparing the results with those obtained with an ordinarily coated diode laser with a 1000-microm-wide emitter we show that antireflection coating on the front facet is decisive for this improvement in the beam quality. 相似文献
60.