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101.
    
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that requires further pathological elucidation to establish effective treatment strategies. We previously showed that amyloid β (Aβ) toxic conformer with a turn at positions 22–23 is essential for forming highly toxic oligomers. In the present study, we evaluated phenotypic changes with aging in AD model AppNL-P-F/NL-P-F (NL-P-F) mice with Swedish mutation (NL), Iberian mutation (F), and mutation (P) overproducing E22P-Aβ, a mimic of toxic conformer utilizing the knock-in technique. Furthermore, the role of the toxic conformer in AD pathology was investigated. NL-P-F mice produced soluble toxic conformers from an early age. They showed impaired synaptic plasticity, glial cell activation, and cognitive decline, followed by the accumulation of Aβ plaques and tau hyperphosphorylation. In addition, the protein expression of hypoxia-inducible factor (HIF)-1α was increased, and gene expression of HIF-3α was decreased in NL-P-F mice. HIF dysregulation due to the production of soluble toxic conformers may be involved in AD pathology in NL-P-F mice. This study could reveal the role of a highly toxic Aβ on AD pathogenesis, thereby contributing to the development of a novel therapeutic strategy targeting the toxic conformer.  相似文献   
102.
An investigation is made into traverse truing of diamond grinding wheels using various truing grit types, grit sizes and truing parameters. Geometry and kinematics of the truing contact are modeled. Specific energies are found to depend on truing-grit size but not on truing parameters, indicating little to no size effect. Removal mechanisms are analyzed via SEM examination of diamond- and truing-wheel swarf. A fundamental relationship is established relating the truing compliance number to the truing efficiency, which encompasses truing parameters and truing- and diamond-grit sizes. Recommendations are made for optimum conditions to minimize force-constrained truing time.  相似文献   
103.
The high lateral resolution of spin-polarized scanning tunneling microscopy allows new insights into the spin structure of antiferromagnets on the nanometer range. We demonstrate the capability to image a well-defined in-plane component of the sample spin polarization and discuss the spin structure of antiferromagnetic bct Mn in contact with the ferromagnetic Fe(001) substrate. Mn atoms couple ferromagnetically within a Mn atomic plane, while normal to the surface a layer-wise antiferromagnetic order was found. Magnetic frustrations arise in this system at Fe substrate steps at the interface, where topologically induced 180 degrees domain walls are created in the Mn film. A clear widening of the enforced domain walls with increasing Mn thickness was found. The measured widths could be fitted with a linear function and are explained on the basis of a Heisenberg model.  相似文献   
104.
Reports an error in A clash of bottom-up and top-down processes in visual search: The reversed letter effect revisited by Li Zhaoping and Uta Frith (Journal of Experimental Psychology: Human Perception and Performance, np). The authors have requested a number of corrections. The corrections are given in the erratum. (The following abstract of the original article appeared in record 2011-09719-001.) It is harder to find the letter “N” among its mirror reversals than vice versa, an inconvenient finding for bottom-up saliency accounts based on primary visual cortex (V1) mechanisms. However, in line with this account, we found that in dense search arrays, gaze first landed on either target equally fast. Remarkably, after first landing, gaze often strayed away again and target report was delayed. This delay was longer for target “N” We suggest that the delay arose because bottom-up saliency clashed with top-down shape recognition. Thus, although gaze landed accurately and quickly to the distinctive feature in the target shape (the orientation of the diagonal bar in “N” or “И”), the identical zigzag shape of target and distractors was registered, leading to temporary confusion. In sparser search arrays with smaller set sizes, top-down target shape recognition occurs earlier and bottom-up saliency is weaker. The clash in this case causes search asymmetry even before target location at first gaze landing. Our findings rule out previous suggestions that search asymmetry stems from stronger preattentive salience for the reversed target and/or faster rejection of familiar distractors. (PsycINFO Database Record (c) 2011 APA, all rights reserved)  相似文献   
105.
We report on participatory design activities within the PoliTeam project, a large project which introduces groupware into the German government. Working with a representative small group of users in different worksites, an existing system was adapted to user and organizational needs, with the plan to improve and expand the system to a large scale. We integrated new approaches of user advocacy and osmosis with an evolutionary cycling process. User advocates and osmosis were techniques used to explore the users' needs during actual system use. These techniques were incorporated into the system development. In this paper, we present experiences with this approach and reflect on its impact on the design process from the designers' point of view.  相似文献   
106.
Recent investigations indicate the relevance of extracellular polymeric substances (EPS) in terms of fouling of low-pressure membranes in advanced wastewater treatment. In this study, the high impact of the macromolecular fraction of effluent organic matter on fouling was confirmed in cross-flow ultrafiltration experiments using secondary effluent with and without autochthonous biopolymers. A method for the extraction of a natural mixture of EPS derived from the bacterium Sinorhizobium sp. is presented. Ultrafiltration of solutions of this bacterial EPS extract revealed a correlation between the concentration of EPS and the loss of permeate flux. However, in ultrafiltration tests using extracted bacterial EPS in a model solution as well as in secondary effluent without autochthonous biopolymers, the extent of membrane fouling was not identical with the fouling provoked by secondary effluent organic matter, although the biopolymer concentrations were comparable. The differences in the fouling behaviour of the extracted bacterial EPS and effluent organic matter are considered to be due to different compositions of the biopolymer fraction in terms of proteins, polysaccharides, and other organic colloids, indicating a particular impact of proteins on ultrafiltration membrane fouling.  相似文献   
107.
This paper analyzes the 1992 and 2003 US Commercial Buildings Energy Consumption Survey microdata files to show the extent to which certain heating, cooling, lighting, and window technologies are entering use, and the resulting impacts on the intensity of energy use. Excepting the case of fluorescent lights, no technology dominates the entire market but instead each conquers a specific niche. Most of the buildings in which these technologies are installed do not have lower-than-average energy intensity, measured as annual energy use per square meter of floor space. The exceptional technology that does measurably correlate with reduced energy intensity is daylighting. These results suggest that technologies are adopted to serve comfort or quality objectives rather than to save energy, or that buildings’ users confound the designers’ intentions. Decision makers thus should improve operating and maintenance practices, invest in building commissioning, and rely more heavily on passive design features to save energy.  相似文献   
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Suspension plasma-sprayed coatings are produced using fine-grained feedstock. This allows to control the porosity and to achieve low thermal conductivity which makes the coatings attractive as topcoats in thermal barrier coatings (TBCs). Used in gas turbine applications, TBCs are exposed to high temperature exhaust gases which lead to microstructure alterations. In order to obtain coatings with optimized thermomechanical properties, microstructure alterations like closing of pores and opening of cracks have to be taken into account. Hence, in this study, TBC topcoats consisting of 4 mol.% yttria-stabilized zirconia were heat-treated in air at 1150 °C and thereafter the coating porosity was investigated using image analysis (IA) and nuclear magnetic resonance (NMR) cryoporometry. Both IA and NMR cryoporometry showed that the porosity changed as a result of the heat treatment for all investigated coatings. In fact, both techniques showed that the fine porosity decreased as a result of the heat treatment, while IA also showed an increase in the coarse porosity. When studying the coatings using scanning electron microscopy, it was noticed that finer pores and cracks disappeared and larger pores grew slightly and achieved a more distinct shape as the material seemed to become more compact.  相似文献   
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