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Although the selective excitatory amino acid transporter subtype 1 (EAAT1) inhibitor UCPH‐101 has become a standard pharmacological tool compound for in vitro and ex vivo studies in the EAAT research field, its inability to penetrate the blood–brain barrier makes it unsuitable for in vivo studies. In the present study, per os (p.o.) administration (40 mg kg?1) of the closely related analogue UCPH‐102 in rats yielded respective plasma and brain concentrations of 10.5 and 6.67 μm after 1 h. Three analogue series were designed and synthesized to improve the bioavailability profile of UCPH‐102, but none displayed substantially improved properties in this respect. In vitro profiling of UCPH‐102 (10 μm ) at 51 central nervous system targets in radioligand binding assays strongly suggests that the compound is completely selective for EAAT1. Finally, in a rodent locomotor model, p.o. administration of UCPH‐102 (20 mg kg?1) did not induce acute effects or any visible changes in behavior.  相似文献   
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The ability to produce offspring from animals otherwise incapable of reproduction has important implications in the equine. Routinely, male equines are electively castrated to produce animals (geldings) that are more easily managed and handled. These animals are then much more conveniently and safety used in various competitions such as cutting, reining, polo, roping, and racing. The ability to recover the genetics of animals that either prematurely die or die prior to sufficient impact of valuable genomics is an important consideration in the horse.  相似文献   
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The numerical performance of lattice-based adaptive signal processing algorithms is shown to involve the conditioning of a 2×2 matrix whose off-diagonal elements contain reflection coefficients. Degraded algorithmic performance for the a posteriori recursive least squares lattice (RLSL) is shown to be attributed to the ill-conditioning of this matrix, Theoretical results are given which may be used to separate the conditioning of the underlying problem from issues concerning algorithmic stability. Although the results are not restricted to the all-pole case, for simplicity the authors make use of this well understood example since the condition number of the autocorrelation matrix will become arbitrarily close to singularity as the poles of an all-pole filter approach the unit circle. For a second-order prediction problem, four case studies of varying conditioning are provided which demonstrate the appropriateness of the theoretical bounds which analytically describe the sensitivity to perturbations in the residual update recursions. The paper illustrates the use of numerical linear algebra analysis techniques to better understand the numerical performance of algorithms in signal processing as well as emphasising that numerical performance is a function of the problem's conditioning as well as algorithmic stability  相似文献   
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681 usable questionnaire returns were received from PhD psychologist respondents. Since completing the language requirements 65% or almost ? of the cases had not read a single item (article or book). "The median number of items read in French, German, Spanish, and Russian was 0." 70% made no oral use of the languages. There is an "extreme incongruity between input and output" in the study of foreign languages at the PhD level. Alternative solutions are proposed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)  相似文献   
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Subtype‐selective ligands are of great interest to the scientific community, as they provide a tool for investigating the function of one receptor or transporter subtype when functioning in its native environment. Several 4‐substituted (S)‐glutamate (Glu) analogues were synthesized, and altogether this approach has provided important insight into the structure–activity relationships (SAR) for ionotropic and metabotropic glutamate receptors (iGluRs and mGluRs), as well as the excitatory amino acid transporters (EAATs). In this work, three 4,4‐disubstituted Glu analogues 1 – 3 , which are hybrid structures of important 4‐substituted Glu analogues 4 – 8 , were investigated at iGluRs and EAATs. Collectively, their pharmacological profiles add new and valuable information to the SAR for the iGluRs and EAAT1–3.  相似文献   
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Impermeable atomic membranes from graphene sheets   总被引:4,自引:0,他引:4  
We demonstrate that a monolayer graphene membrane is impermeable to standard gases including helium. By applying a pressure difference across the membrane, we measure both the elastic constants and the mass of a single layer of graphene. This pressurized graphene membrane is the world's thinnest balloon and provides a unique separation barrier between 2 distinct regions that is only one atom thick.  相似文献   
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Matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) provides localized information about the molecular content of a tissue sample. To derive reliable conclusions from MSI data, it is necessary to implement appropriate processing steps in order to compare peak intensities across the different pixels comprising the image. Here, we review commonly used normalization methods, and propose a rational data processing strategy, for robust evaluation and modeling of MSI data. The approach includes newly developed heuristic methods for selecting biologically relevant peaks and pixels to reduce the size of a data set and remove the influence of the applied MALDI matrix. The methods are demonstrated on a MALDI MSI data set of a sagittal section of rat brain (4750 bins, m/z = 50-1000, 111 × 185 pixels) and the proposed preferred normalization method uses the median intensity of selected peaks, which were determined to be independent of the MALDI matrix. This was found to effectively compensate for a range of known limitations associated with the MALDI process and irregularities in MS image sampling routines. This new approach is relevant for processing of all MALDI MSI data sets, and thus likely to have impact in biomarker profiling, preclinical drug distribution studies, and studies addressing underlying molecular mechanisms of tissue pathology.  相似文献   
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