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41.
    
Our objective is to reveal the molecular mechanism of the anti-inflammatory action of low-molecular-weight heparin (LMWH) based on its influence on the activity of two key cytokines, IFNγ and IL-6. The mechanism of heparin binding to IFNγ and IL-6 and the resulting inhibition of their activity were studied by means of extensive molecular-dynamics simulations. The effect of LMWH on IFNγ signalling inside stimulated WISH cells was investigated by measuring its antiproliferative activity and the translocation of phosphorylated STAT1 in the nucleus. We found that LMWH binds with high affinity to IFNγ and is able to fully inhibit the interaction with its cellular receptor. It also influences the biological activity of IL-6 by binding to either IL-6 or IL-6/IL-6Rα, thus preventing the formation of the IL-6/IL-6Rα/gp130 signalling complex. These findings shed light on the molecular mechanism of the anti-inflammatory action of LMWH and underpin its ability to influence favourably conditions characterised by overexpression of these two cytokines. Such conditions are not only associated with autoimmune diseases, but also with inflammatory processes, in particular with COVID-19. Our results put forward heparin as a promising means for the prevention and suppression of severe CRS and encourage further investigations on its applicability as an anti-inflammatory agent.  相似文献   
42.
Previous studies of chemoreceptive behavior in vipers suggest that snakes focus on the scent of envenomated tissue to track their prey following envenomation. Other studies have indicated a correlation between qualitative differences in venom biochemistry and geographic variation in diet. The North American copperhead (Agkistrodon contortrix) varies geographically in diet and venom biochemistry; snakes were collected from three populations (Kansas, Texas, and Louisiana) that are known to have different prey preferences. Behavioral experiments were conducted to assess whether copperheads preferred envenomated prey more than nonenvenomated prey, as do other species of vipers studied thus far. Additional experiments tested the ability of copperheads to distinguish between envenomated prey from different geographic populations, and between geographic populations of copperheads and two other species of viper. Results indicated that copperheads prefer envenomated prey to nonenvenomated prey. In envenomated-prey discrimination experiments, copperheads distinguished between envenomated prey from different geographic populations, and some snakes distinguished envenomated prey of A. contortrix from those of A. piscivorus and Sistrurus catenatus. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) was used to study the variation of venom biochemistry in this species and two other taxa (A. piscivorus and S. catenatus), and confirmed intraspecific and interspecific variation of venom proteins. Relative potency of the venom from different populations as indicated by time to immobilization experiments was in the order: Louisiana >Texas > Kansas. The relative potency of the venom from each population matched the order of preference in the chemoreception experiments. These results suggest that chemoreception is sensitive to subtle differences in venom biochemistry and may reflect adaptation to improve efficiency of finding envenomated prey.  相似文献   
43.
The theoretical calculations of the mass transfer rate are based on a model which considers a nonlinear adsorption isotherms and simultaneous resistance to mass transfer in The pore adsorbent and the convective mass transfer. Numerical solutions to the diffusive-convective-controlled adsorption and desorption processes are calculated for the Langmuir and rectangular adsorption isotherms. It is shown that for the rectangular adsorption isotherm the adsorption kinetics is governed by the diffusive-convective mass transfer over a wide range of times and the desorption kinetics is irreversible process. The equations are derived to calculate from the experimental kinetics data: (a) the coefficient diffusion in the pore adsorbent, (b) the relaxation times characterizing the adsorption and desorption processes, and (c) the times needed to reach the quasiequilibrium state for the adsorption and desorption processes.  相似文献   
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N. R. Brown and R. S. Siegler (1996) found that training participants on a subset of country populations improved estimations for novel transfer country populations, an effect called seeding that remained intact over time. They attributed this effect to the abstraction by participants of a general metric framework for estimating populations not dependent on specific country anchors. In a series of 3 follow-up experiments, the authors found that training on seed populations produces both general metric information and durable specific country information. Moreover, minimal amounts of general (mean or range of populations) or specific (1 or 3 countries) information made available for inspection while estimating produced a significant seeding effect. Retention over long intervals was facilitated by both presenting 3 seed countries as opposed to 1 and providing names for the seed countries. (PsycINFO Database Record (c) 2010 APA, all rights reserved)  相似文献   
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We show from analytical analysis of the basic stimulated Brillouin scattering (SBS) equations in the time domain that the SBS amplification process does not amplify an external Stokes pulse and therefore cannot induce group delay of the Stokes pulse as claimed in the literature. Rather, the delayed output Stokes pulse is the pump radiation reflected by the induced acoustic wave, the amplitude of which determines the rate of the amplification process and time delay of the pulse. The latter is predominantly a consequence of the SBS buildup process determined by the inertia of the acoustic wave excitation. Analytical solutions of the SBS equations in the frequency domain show that spectral broadening of the pump radiation leads to only negligible broadening of the SBS spectral bandwidth and so does not provide an effective means to achieve broadband pulse delay.  相似文献   
48.
A numerical analysis of laminar natural convection with entropy generation in a partially heated open triangular cavity filled with a Cu-water nanofluid has been carried out. Mathematical model including partial differential equations and boundary conditions has been solved by using finite difference method. Particular efforts have been focused on the effects of Rayleigh number, nanoparticles volume fraction and position of the local heater on streamlines, isotherms, local entropy generation as well as local and average Nusselt number, average Bejan number, average entropy generation and fluid flow rate. Obtained results have demonstrated that the heat transfer enhancement and fluid flow attenuation with nanoparticles volume fraction, mainly for high values of Rayleigh number.  相似文献   
49.
The goal of this study was to evaluate binding of four targets of biodefense interest to immobilized antimicrobial peptides (AMPs) in biosensor assays. Polymyxins B and E, melittin, cecropins A, B, and P, parasin, bactenecin and magainin-1, as well as control antibodies, were used as capture molecules for detection of Cy3-labeled Venezuelan equine encephalitis virus (VEE), vaccinia virus, C. burnetti and B. melitensis. Although VEE, vaccinia virus and C. burnetti did not show any binding activity to their corresponding capture antibodies, B. melitensis bound to immobilized anti-Brucella monoclonal antibodies. The majority of the immobilized AMPs included in this study bound labeled VEE, vaccinia virus and C. burnetti in a concentration-dependent manner, and B. melitensis bound to polymyxin B, polymyxin E, and bactenecin. No binding was observed on immobilized magainin-1. In contrast to all bacterial targets tested to date, VEE and vaccinia virus demonstrated similar patterns of binding to all peptides. While the direct assay is generally replaced by a sandwich assay for analysis of real-world samples, direct binding experiments are commonly used to characterize specificity and sensitivity of binding molecules. In this case, they clearly demonstrate the capability of AMPs as recognition molecules for four biothreat agents.  相似文献   
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