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661.
In this study, new refractory coatings based on synthesized cordierite for the casting applications were developed. The investigation included starting raw materials characterization, synthesis of the cordierite, design of the refractory coating as final product, and its application testing. The obtained results pointed out that coating suspension sediment stability was crucial quality parameter. Design and optimization of the coatings composition, with controlled rheological properties included, were achieved by application of different coating components, namely different suspension agents and by alteration of the coating production procedure. Cordierite, used as filler, was obtained by means of synthesis in the solid‐state reaction on the basis of talc, kaolin, and alumina. The investigation showed that the application of these particular types of water/alcohol‐based coatings has positive influence on surface quality and structural and mechanical properties of the castings of aluminum alloys obtained by casting into sand molds by means of evaporable models method, that is, evaporate pattern casting process.  相似文献   
662.
Expansion of the structural diversity of peptide antibiotics was performed through two different methods. Supplementation‐based incorporation (SPI) and stop‐codon suppression (SCS) approaches were used for co‐translational incorporation of isostructural and orthogonal noncanonical amino acids (ncAAs) into the lasso peptide capistruin. Two ncAAs were employed for the SPI method and five for the SCS method; each of them probing the incorporation of ncAAs in strategic positions of the molecule. Evaluation of the assembly by HR‐ESI‐MS proved more successful for the SCS method. Bio‐orthogonal chemistry was used for post‐biosynthetic modification of capistruin congener Cap_Alk10 containing the ncAA Alk (Nε‐Alloc‐L ‐lysine) instead of Ala. A second‐generation Hoveyda–Grubbs catalyst was used for an in vitro metathesis reaction with Cap_Alk10 and an allyl alcohol, which offers options for post‐biosynthetic modifications. The use of synthetic biology allows for the in vivo production of new peptide‐based antibiotics from an expanded amino acid repertoire.  相似文献   
663.
The kinetics of plant stanol uptake and routing in 8‐week‐old C57BL/6J mice were determined after a plant stanol ester gavage. In addition, acute changes in intestinal and hepatic gene expression were investigated. Mice were fed a plant sterol/stanol poor diet from weaning. At the age of 8 weeks, they received an oral gavage consisting of 0.25 mg cholesterol + 50 mg plant stanol esters dissolved in olive oil. Animals were euthanized at different time points. In a second comparable set‐up, mesenteric lymph‐cannulated versus sham‐operated mice received the same oral gavage, which was now deuterium labeled. Intestinal and hepatic sitostanol concentrations increased within 15 min post‐gavage. This rapid hepatic appearance was absent in lymph‐cannulated mice, suggesting a very fast lymph‐mediated uptake. Hepatic mRNA expression of SREBP2 and its target genes rapidly decreased, whereas expression of LXR target genes increased. The intestinal SREBP2 pathway was increased, whereas the expression of LXR target genes hardly changed. The fivefold and sixfold increased expression of intestinal LDLr and PCSK9 is suggestive of TICE activation. We conclude that in C57BL/6J mice plant stanol kinetics are fast, and affect intestinal and hepatic gene expression within 15 min postprandial after lymph‐mediated uptake.  相似文献   
664.
Pickering emulsions have received increasing interest in many fields of application recently. In designing Pickering emulsion properties, focus is typically laid on composition whereas the preparation process as another possible leverage is not considered in detail. Here, Pickering emulsions of constant composition were prepared using two dispersing heads of a rotor-stator homogenizer and compared in terms of Sauter mean diameters and rheology. It was found that the ratio of tip speed and gap width between rotor and stator is a better correlating parameter than tip speed only.  相似文献   
665.
    
Despite the high economic and nutritional value as major positive aspects, olive oil production has an unfavourable side, which is the negative environmental impact caused by the generation of significant amounts of liquid and solid wastes. Therefore, the implementation of sustainable technologies to add value to the olive oil production process is a matter of great interest. This study aimed to review novel solutions dealing with the utilisation of olive oil production by-products while taking into account sustainable waste management options. The most promising technologies for the production of high-added value products from olive oil production by-products have been described with a special attention to the sustainable nonthermal technologies for the extraction of bioactive phenolic compounds, and the key findings of such investigations were reviewed. All described technologies are environmentally friendly and show great potential. Nevertheless, further researches are required to optimise and increase their applicability.  相似文献   
666.
667.
    
ANCA-associated vasculitis (AAV) comprises granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA). While systemic vasculitis is a hallmark of all AAV, GPA is characterized by extravascular granulomatous inflammation, preferentially affecting the respiratory tract. The mechanisms underlying the emergence of neutrophilic microabscesses; the appearance of multinucleated giant cells; and subsequent granuloma formation, finally leading to scarred or destroyed tissue in GPA, are still incompletely understood. This review summarizes findings describing the presence and function of molecules and cells contributing to granulomatous inflammation in the respiratory tract and to renal inflammation observed in GPA. In addition, factors affecting or promoting the development of granulomatous inflammation such as microbial infections, the nasal microbiome, and the release of damage-associated molecular patterns (DAMP) are discussed. Further, on the basis of numerous results, we argue that, in situ, various ways of exposure linked with a high number of infiltrating proteinase 3 (PR3)- and myeloperoxidase (MPO)-expressing leukocytes lower the threshold for the presentation of an altered PR3 and possibly also of MPO, provoking the local development of ANCA autoimmune responses, aided by the formation of ectopic lymphoid structures. Although extravascular granulomatous inflammation is unique to GPA, similar molecular and cellular patterns can be found in both the respiratory tract and kidney tissue of GPA and MPA patients; for example, the antimicrobial peptide LL37, CD163+ macrophages, or regulatory T cells. Therefore, we postulate that granulomatous inflammation in GPA or PR3-AAV is intertwined with autoimmune and destructive mechanisms also seen at other sites.  相似文献   
668.
    
Two-photon microscopy enables monitoring cellular dynamics and communication in complex systems, within a genuine environment, such as living tissues and, even, living organisms. Particularly, its application to understand cellular interactions in the immune system has brought unique insights into pathophysiologic processes in vivo. Simultaneous multiplexed imaging is required to understand the dynamic orchestration of the multiple cellular and non-cellular tissue compartments defining immune responses. Here, we present an improvement of our previously developed method, which allowed us to achieve multiplexed dynamic intravital two-photon imaging, by using a synergistic strategy. This strategy combines a spectrally broad range of fluorophore emissions, a wave-mixing concept for simultaneous excitation of all targeted fluorophores, and an unmixing algorithm based on the calculation of spectral similarities with previously measured fluorophore fingerprints. The improvement of the similarity spectral unmixing algorithm here described is based on dimensionality reduction of the mixing matrix. We demonstrate its superior performance in the correct pixel-based assignment of probes to tissue compartments labeled by single fluorophores with similar spectral fingerprints, as compared to the full-dimensional similarity spectral unmixing approach.  相似文献   
669.
    
Background: Reduction of the Sphingosine-1-phosphate (S1P) degrading enzyme S1P lyase 1 (SGPL1) initiates colorectal cancer progression with parallel loss of colon function in mice. We aimed to investigate the effect of SGPL1 knockout on the stem cell niche in these mice. Methods: We performed immunohistochemical and multi-fluorescence imaging on tissue sections of wildtype and SGPL1 knockout colons under disease conditions. Furthermore, we generated SGPL1 knockout DLD-1 cells (SGPL1−/−M.Ex1) using CRISPR/Cas9 and characterized cell cycle and AKT signaling pathway via Western blot, immunofluorescence, and FACS analysis. Results: SGPL1 knockout mice were absent of anti-Ki-67 staining in the stem cell niche under disease conditions. This was accompanied by an increase of the negative cell cycle regulator FOXO3 and attenuation of CDK2 activity. SGPL1−/−M.Ex1 cells show a similar FOXO3 increase but no arrest of proliferation, although we found a suppression of the PDK1/AKT signaling pathway, a prolonged G1-phase, and reduced stem cell markers. Conclusions: While already established colon cancer cells find escape mechanisms from cell cycle arrest, in vivo SGPL1 knockout in the colon stem cell niche during progression of colorectal cancer can contribute to cell cycle quiescence. Thus, we propose a new function of the S1P lyase 1 in stemness.  相似文献   
670.
    
Neuroinflammation is a pathological hallmark of several neurodegenerative disorders and plays a key role in the pathogenesis of amyotrophic lateral sclerosis (ALS). It has been implicated as driver of disease progression and is observed in ALS patients, as well as in the transgenic SOD1G93A mouse model. Here, we explore and validate the therapeutic potential of the d-enantiomeric peptide RD2RD2 upon oral administration in SOD1G93A mice. Transgenic mice were treated daily with RD2RD2 or placebo for 10 weeks and phenotype progression was followed with several behavioural tests. At the end of the study, plasma cytokine levels and glia cell markers in brain and spinal cord were analysed. Treatment resulted in a significantly increased performance in behavioural and motor coordination tests and a decelerated neurodegenerative phenotype in RD2RD2-treated SOD1G93A mice. Additionally, we observed retardation of the average disease onset. Treatment of SOD1G93A mice led to significant reduction in glial cell activation and a rescue of neurons. Analysis of plasma revealed normalisation of several cytokines in samples of RD2RD2-treated SOD1G93A mice towards the levels of non-transgenic mice. In conclusion, these findings qualify RD2RD2 to be considered for further development and testing towards a disease modifying ALS treatment.  相似文献   
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