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101.
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Characterization of new pharmacological targets is a promising approach in research of neurorepair mechanisms. The G protein-coupled receptor 17 (GPR17) has recently been proposed as an interesting pharmacological target, e.g., in neuroregenerative processes. Using the well-established ex vivo model of organotypic slice co-cultures of the mesocortical dopaminergic system (prefrontal cortex (PFC) and substantia nigra/ventral tegmental area (SN/VTA) complex), the influence of GPR17 ligands on neurite outgrowth from SN/VTA to the PFC was investigated. The growth-promoting effects of Montelukast (MTK; GPR17- and cysteinyl-leukotriene receptor antagonist), the glial cell line-derived neurotrophic factor (GDNF) and of two potent, selective GPR17 agonists (PSB-16484 and PSB-16282) were characterized. Treatment with MTK resulted in a significant increase in mean neurite density, comparable with the effects of GDNF. The combination of MTK and GPR17 agonist PSB-16484 significantly inhibited neuronal growth. qPCR studies revealed an MTK-induced elevated mRNA-expression of genes relevant for neuronal growth. Immunofluorescence labelling showed a marked expression of GPR17 on NG2-positive glia. Western blot and RT-qPCR analysis of untreated cultures suggest a time-dependent, injury-induced stimulation of GPR17. In conclusion, MTK was identified as a stimulator of neurite fibre outgrowth, mediating its effects through GPR17, highlighting GPR17 as an interesting therapeutic target in neuronal regeneration.  相似文献   
103.
The research and demonstration project, DEMO-SPK, a model project under the German Mobility and Fuel Strategy (MFS), investigated the use of renewable kerosene at the Leipzig/Halle airport. Its primary goal was to examine and verify the behavior of blends consisting of several types of renewable kerosene and fossil JET A-1, under the realistic supply conditions of a major airport. The project demonstrated that the supply chain for multiblend JET A-1 was technically feasible and that the fuel could be used without requiring any changes in the normal operating procedures. The project also confirmed that the use of multiblend JET A-1 resulted in a 30–60% reduction in particulate emissions for ground operations and a reduction in CO2 equivalents, compared with pure fossil JET A-1.  相似文献   
104.
This study provides the influence of different heat exchanger internals (helical pipe coils, heating plugs, pipe registers) and reactor bottom shapes (torispherical/dished (Kloepper‐shape), hemispherical, and flat) on the flow field, the turbulent kinetic energy, and the ratio of tangential flow in stirred vessels, based on extensive stereo PIV measurement series in refractive index‐matched, optically completely accessible systems. The investigations impressively show advantages and disadvantages of the various equipment, which have a massive influence on both heat transport and the flow.  相似文献   
105.
Efficient use of material and energy flows increases the competitiveness of manufacturing companies and saves the environment at the same time. In order to significantly reduce the use of non-renewable materials and energy, a change from a linear to a closed-loop production process is necessary. In recent years, various closed-loop strategies have been developed, implemented or are in the process of being implemented. In this paper, a brief overview of approaches for a circular economy in the process industry is given.  相似文献   
106.
Abstract

The paper explores the interplay of elaborate light and sound technologies used in the worship services of Lakewood Church in Houston, Texas. During the renovation and reconstruction of the church venue from former basketball stadium to church auditorium, the church hired professional companies to design and outfit the huge 16,000 seat auditorium in order to create a worship space, which simultaneously is meant to serve as a meeting space for the congregation and as an intimate place for a personal encounter with God. Worship services at Lakewood Church are multi-sensory events in which lights on the ceiling, in the auditorium, and on stage interplay with sound, vision, and space in order to structure the worship service and to mediate divine presence. The analysis is based on fieldwork data acquired on site and textual data drawn from portfolios of the technological companies involved in the reconstruction and outfitting of the church auditorium. I argue that despite the capaciousness of the space an atmosphere of intimacy is created through a specific lighting scheme that departs from traditional church lighting practices.  相似文献   
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108.
Drug formulations based on lipids can enable a significantly better delivery of a pharmaceutically active substance and thus enhance their bioavailability. However, natural fats and oils usually have properties, which do not allow their direct use for drug delivery. Therefore, we have modified palm kernel oil (PKO) and shea butter (SB) via lipase‐catalyzed transesterification using either glycerol – to create a diglyceride‐enriched lipid – or using hexanoic acid via acidolysis – to alter their fatty acid composition – and hence to improve drug solubility of Celecoxib serving as model compound. The most suitable enzyme was immobilized Thermomyces lanuginosus lipase (Novozyme TL IM). The solubility of Celecoxib as determined in SB, pharmaceutical grade SB, glycerol‐modified SB, hexanoic acid‐modified SB, PKO, glycerol‐modified PKO, and hexanoic acid‐modified PKO. Incorporation of one or two equivalents of hexanoic acid enabled higher Celecoxib solubilization than the diglyceride rich oil. Although structured SB and PKO (15.8 ± 0.4 mg mL?1) do not differ significantly (p < 0.05) as per the amount of Celecoxib dissolved, the use of the modified oils enhanced Celecoxib solubility in SB (15.5 ± 1.3 mg mL?1) in comparison to shea butter (7.9 ± 0.5 mg mL?1). The lipase‐catalyzed modification also improved the miscibility of the oils with surfactants such as Tween 20 and resulted in reduced droplet sizes (<70 nm at oil/surfactant ratios of 1:2 and 1:1) and reduced polydispersity index values of the resulting emulsions. Practical Application: The structured triglycerides synthesized in this work on the basis of natural shea butter oils could function as suppository bases and oil phase in oral and parenteral lipid‐based formulations for improving the solubility and absorption of poorly soluble drugs. As various lipases with distinct selectivity are available for the enzymatic synthesis of structured triglycerides and useful for this purpose, further tailor‐designed formations should be accessible. With the aim of developing novel lipid drug delivery matrices palm kernel oil (PKO) and shea butter (SB) were modified via lipase‐catalyzed transesterification to alter their fatty acid composition and hence to improve drug solubility of the model compound Celecoxib. Incorporation of one or two equivalents of hexanoic acid enabled better Celecoxib solubilization than the diglyceride‐rich oil. Overall, the successful modification process yielded structured lipids with promising miscibility with selected surfactants and potential enhancement of Celecoxib solubility and thus represents a promising approach for the development of novel safe and effective lipid‐based delivery systems.
  相似文献   
109.
Mass spectrometry-based metabolomics   总被引:18,自引:0,他引:18  
This review presents an overview of the dynamically developing field of mass spectrometry-based metabolomics. Metabolomics aims at the comprehensive and quantitative analysis of wide arrays of metabolites in biological samples. These numerous analytes have very diverse physico-chemical properties and occur at different abundance levels. Consequently, comprehensive metabolomics investigations are primarily a challenge for analytical chemistry and specifically mass spectrometry has vast potential as a tool for this type of investigation. Metabolomics require special approaches for sample preparation, separation, and mass spectrometric analysis. Current examples of those approaches are described in this review. It primarily focuses on metabolic fingerprinting, a technique that analyzes all detectable analytes in a given sample with subsequent classification of samples and identification of differentially expressed metabolites, which define the sample classes. To perform this complex task, data analysis tools, metabolite libraries, and databases are required. Therefore, recent advances in metabolomics bioinformatics are also discussed.  相似文献   
110.
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