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961.
In continuing efforts to synthesize potent, anti-inflammatory steroids devoid of systemic side effects, methyl 9 alpha-fluoro-11 beta,17 alpha,21-trihydroxy-3,20-dioxo-pregna-1,4-diene-16 alpha-carboxylate (FP16CM) and its 21-acetate derivative (FP16CMAc) were recently synthesized and screened in animal models of inflammation. The compounds have now been assessed for high-affinity glucocorticoid receptor binding and glucocorticoid-mediated inhibition of nitric oxide (NO) generation in an in vitro RAW 264.7 macrophage cell culture system. Relative potencies for glucocorticoid receptor binding were 1, 1.7, and 2.4 for prednisone (P) (IC50 = 287 nM), FP16CM, and FP16CMAc, respectively. Concomitant relative potencies for inhibition of NO generation by macrophages stimulated with lipopolysaccharide were 1, 0.92 and 1.9 for P (IC50 = 126 nM), FP16CM, and FP16CMAc, respectively. Collectively, results suggest that the novel antedrugs are active anti-inflammatory agents. The 9 alpha-fluoro and 21-acetate substituent may contribute to enhanced topical potency, increased receptor binding affinity and inhibitory effects on NO generation. Inhibition of vasoactive NO may be one anti-inflammatory action of the steroidal antedrugs in vivo. Collectively, results suggest that these agents may be useful for topical application in allergic/inflammatory diseases. 相似文献
962.
963.
A simple strategy using selective codon optimization was devised to express mouse c-Fos protein in high levels in E. coli. Ten arginine codons located in the basic region were optimized to achieve high levels of protein expression. The c-Fos protein was purified to near homogeneity and was demonstrated to be biologically active by assaying its several biological activities. 相似文献
964.
965.
The extracts of Coptidis japonica (rhizoma), Eugenia caryophyllata (flower), Rheum palmatum (rhizoma), Magnolia officinalis (cortex) and Rhusjavanica (galla rhois) potently inhibited the growth of Helicobacter pylori (HP). However, these herbal extracts showed no inhibitory effect on HP urease except Galla rhois. Among the components separated from active herbal extracts by silica gel column chromatography, the inhibitory effects of decursinol angelate and decursin on the growth of HP were the most potent, followed by magnolol, berberine, cinnamic acid, decursinol and gallic acid. Minimum inhibitory concentrations (MICs) of decursin and decursinol angelate were 6-20 microg/ml. 相似文献
966.
The purpose of this study was to explore gender differences of medication use in a random sample of community-dwelling elderly subjects (N = 791). The average number of different medications in women (N = 578) was higher than in men (N = 213) (4.0 vs. 3.5, age corrected ratio 1.2, 95% confidence interval, 1.0-1.3). However, despite this relatively small difference in number of medications there was a major gender difference in the pattern of medications used. Compared to men, women had a higher use of benzodiazepines (risk ratio 1.7, 95% confidence interval, 1.3-2.3), diuretics (1.5, 1.1-2.0), nonsteroidal antiinflammatory agents (1.7, 1.2-2.3), and anti-depressants (2.5, 1.1-5.5), but a lower use of pulmonary (0.5, 0.3-0.9) and gout medications (0.2, 0.1-0.6). These gender differences in medication use can be explained by the fact that compared to men, women have a higher prevalence of non-lethal chronic conditions such as degenerative joint disease and hypertension. However, additional factors such as gender-specific differences in patient or physician behavior are likely to contribute to the observed differences in medication use as well. Overall, 36% of all women and 21% of all men were using benzodiazepines, with 42% of these subjects using long-acting compounds. Furthermore, 24% of all women and 15% of all men reported use of nonsteroidal antiinflammatory agents for which safer medication and non-medication alternatives would be available in many cases. Thus, women had a higher risk of inappropriate medication use than men. On the other hand, the finding that antidepressant use was 3% in men and 7% in women indicates that compared to women, men might be at increased risk for undertreatment of depression. Further causal evaluation of gender differences in both medication use and patient-physician interaction might contribute to detection and reduction of inappropriate drug use in older persons. 相似文献
967.
Triclosan (Irgasan) is a broad spectrum antimicrobial agent used in handsoaps, toothpastes, fabrics, and plastics. It inhibits lipid biosynthesis in Escherichia coli, probably by action upon enoyl reductase (FabI) (McMurry, L.M., Oethinger, M. and Levy, S.B. (1988) Nature 394, 531-532). We report here that overexpression of the multidrug efflux pump locus acrAB, or of marA or soxS, both encoding positive regulators of acrAB, decreased susceptibility to triclosan 2-fold. Deletion of the acrAB locus increased the susceptibility to triclosan approximately 10-fold. Four of five clinical E. coli strains which overexpressed marA or soxS also showed enhanced triclosan resistance. The acrAB locus was involved in the effects of triclosan upon both cell growth rate and cell lysis. 相似文献
968.
Coarse-grained molecular models of the erythrocyte membrane's spectrin cytoskeleton are presented in Monte Carlo simulations of whole cells in micropipette aspiration. The nonlinear chain elasticity and sterics revealed in more microscopic cytoskeleton models (developed in a companion paper; Boey et al., 1998. Biophys. J. 75:1573-1583) are faithfully represented here by two- and three-body effective potentials. The number of degrees of freedom of the system are thereby reduced to a range that is computationally tractable. Three effective models for the triangulated cytoskeleton are developed: two models in which the cytoskeleton is stress-free and does or does not have internal attractive interactions, and a third model in which the cytoskeleton is prestressed in situ. These are employed in direct, finite-temperature simulations of erythrocyte deformation in a micropipette. All three models show reasonable agreement with aspiration measurements made on flaccid human erythrocytes, but the prestressed model alone yields optimal agreement with fluorescence imaging experiments. Ensemble-averaging of nonaxisymmetrical, deformed structures exhibiting anisotropic strain are thus shown to provide an answer to the basic question of how a triangulated mesh such as that of the red cell cytoskeleton deforms in experiment. 相似文献
969.
Tottering mice inherit a recessive mutation of the calcium channel alpha1A subunit that causes ataxia, polyspike discharges, and intermittent dystonic episodes. The calcium channel alpha1A subunit gene encodes the pore-forming protein of P/Q-type voltage-dependent calcium channels and is predominantly expressed in cerebellar granule and Purkinje neurons with moderate expression in hippocampus and inferior colliculus. Because calcium misregulation likely underlies the tottering mouse phenotype, calcium channel blockers were tested for their ability to block the motor episodes. Pharmacologic agents that specifically block L-type voltage-dependent calcium channels, but not P/Q-type calcium channels, prevented the inducible dystonia of tottering mutant mice. Specifically, the dihydropyridines nimodipine, nifedipine, and nitrendipine, the benzothiazepine diltiazem, and the phenylalkylamine verapamil all prevented restraint-induced tottering mouse motor episodes. Conversely, the L-type calcium channel agonist Bay K8644 induced stereotypic tottering mouse dystonic at concentrations significantly below those required to induce seizures in control mice. In situ hybridization demonstrated that L-type calcium channel alpha1C subunit mRNA expression was up-regulated in the Purkinje cells of tottering mice. Radioligand binding with [3H]nitrendipine also revealed a significant increase in the density of L-type calcium channels in tottering mouse cerebellum. These data suggest that although a P/Q-type calcium channel mutation is the primary defect in tottering mice, L-type calcium channels may contribute to the generation of the intermittent dystonia observed in these mice. The susceptibility of L-type calcium channels to voltage-dependent facilitation may promote this abnormal motor phenotype. 相似文献
970.