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排序方式: 共有57条查询结果,搜索用时 15 毫秒
1.
Chambers C Smith F Williams C Marcos S Liu ZH Hayter P Ciaramella G Keighley W Gribbon P Sewing A 《Combinatorial chemistry & high throughput screening》2003,6(4):355-362
The measurement of intracellular calcium fluxes in real time is widely applied within the pharmaceutical industry to measure the activation of G-protein coupled receptors (GPCRhyp;s), either for pharmacological characterisation or to screen for new surrogate ligands. Initially restricted to G(q) coupled GPCRs, the introduction of promiscuous and chimeric G-proteins has further widened the application of these assays. The development of new calcium sensitive dyes and assays has provided sensitive, homogeneous assays which can be readily applied to high throughput screening (HTS). In this paper we describe the full automation of this assay type using a fluorometric imaging plate reader (FLIPR ) integrated into a Beckman/Sagian system to establish a simple robotic system that is well suited for the current medium throughput screening in this area of lead discovery. Using a recently completed HTS we discuss important determinants for FLIPR based screening, highlight some limitations of the current approach, and look at the requirements for future automated systems capable of keeping up with expanding compound files. 相似文献
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Kosikov KM Gorin AA Lu XJ Olson WK Manning GS 《Journal of the American Chemical Society》2002,124(17):4838-4847
DNA dodecamers of the alternating d(CG).d(CG) sequence with six phosphate groups either charge-neutralized or substituted by neutral methylphosphonates across the major or minor groove have been subjected to energy minimization to determine the conformational effect of the asymmetric elimination of phosphate charge. We report bending angles, directions of bending, and detailed structural characteristics such as groove widths and local base-pair parameters. Our principal results are that charge neutralization on one face of the DNA induces significant bending toward the neutralized face, in agreement with theoretical predictions on a simplified model and experimental data on a similar base-pair sequence, and that the DNA conformation averaged over all stereospecific methylphosphonate substitutions is nearly the same as the conformation produced by charge neutralization of the phosphates. Individual isomers, however, cover a wide range of structures, with the magnitude and direction of overall bending sensitive to the precise stereochemical pattern of neutralization. Our simulation does not explicitly contain counterions, and the results therefore suggest that counterions can influence DNA structure by neutralizing the phosphate charge. These data provide new hints into the molecular mechanisms which underlie the deformations of DNA structure induced by the binding of positively charged proteins and other tightly associated cationic species. 相似文献
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K. Wilmański 《Journal of Elasticity》2003,71(1-3):247-261
The paper contains a brief presentation of a macroscopical thermodynamic model of poroelastic materials with many fluid components. A particular emphasis is placed on a Lagrangian formulation of the model and, consequently, on a consistent formulation of field equations on the reference configuration of the skeleton (solid phase of the mixture). It is demonstrated that the model possesses an identical structure as that in the pioneering work of C.A. Truesdell on the continuum mixture of fluids. An issue of porosity as an additional microstructural variable is particularly exposed. 相似文献
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Wilma Neumann Hans‐Ullrich Siehl Klaus‐Peter Zeller Stefan Berger Dieter Sicker 《Chemie in Unserer Zeit》2015,49(3):172-181
Eucalyptol (1,8‐cineol), a cyclic monoterpenoid ether, is the dominant portion of eucalyptus oil, an essential oil of Eucalyptus globulus, accessible by steam distillation of its leaves. Some herbs and spices such as basil and cardamom also contain it as characterising flavour compound. Eucalyptus is a very diverse genus of Myrtaceae naturally occurring in Australia to whom the species have adapted in evolution. Planting Eucalyptus trees outside Australia has both benefits for poor populations and drawbacks. Especially, the enormous water consumption has been criticized. The total impact is doubtful. Eucalyptol is used in flavorings, fragrances, confectionery, cosmetics, cough suppressants, and insect repellents. Higher than normal doses are a hazard. A convenient isolation of eucalyptol from eucalyptus is reported. All analytical spectra were recorded and are reproduced and interpreted either in the main part or in the supporting information. The project is a follow up of the recent book “Classics in Spectroscopy” by S. Berger und D. Sicker (Wiley‐VCH 2009). 相似文献
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A new gas chromatography (GC) method is presented for analysing both the conversion and the enantiomeric excess (e.e.) of samples from alcohol dehydrogenase reactions. The chiral compounds studied were a series of saturated, straight chain alcohols, ranging from 2-butanol to 2-heptanol. The alcohols were converted to the corresponding trifluoroacetylated derivatives by injecting trifluoroacetic anhydride onto the column shortly after injection of the aqueous samples in split-injection mode (1:100) onto a Chiraldex G-TA capillary GC column. Injecting seven hundred aqueous enzymatic reaction mixtures according to the above-mentioned procedure revealed no noticeable loss of column performance. Using the new GC method, conventional sample work-up procedures such as extraction and off-line derivatisation are eliminated and throughput of samples is significantly enhanced. 相似文献
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Margot Bennink Marcel A. Croon Brigitte Kroon Jeroen K. Vermunt 《Advances in Data Analysis and Classification》2016,10(2):139-154
An existing micro–macro method for a single individual-level variable is extended to the multivariate situation by presenting two multilevel latent class models in which multiple discrete individual-level variables are used to explain a group-level outcome. As in the univariate case, the individual-level data are summarized at the group-level by constructing a discrete latent variable at the group level and this group-level latent variable is used as a predictor for the group-level outcome. In the first extension, that is referred to as the Direct model, the multiple individual-level variables are directly used as indicators for the group-level latent variable. In the second extension, referred to as the Indirect model, the multiple individual-level variables are used to construct an individual-level latent variable that is used as an indicator for the group-level latent variable. This implies that the individual-level variables are used indirectly at the group-level. The within- and between components of the (co)varn the individual-level variables are independent in the Direct model, but dependent in the Indirect model. Both models are discussed and illustrated with an empirical data example. 相似文献