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RATIONALE AND OBJECTIVES: Small electrolyte additions to a nonionic contrast medium reduce the risk of ventricular fibrillation (VF) during wedged catheter injection of a contrast medium. The current study was designed to further investigate contrast-medium-induced VF by studying the effect of pretreatment with different antiarrhythmic drugs. METHODS: During a simulated wedged catheter situation, iohexol was injected into the anterior descending branch of the left coronary artery in five open-chest, anesthetized dogs pretreated with lidocaine, propranolol, amiodarone, almokalant, or verapamil. RESULTS: Wedging the catheter for 60 sec did not induce VF. However, all 15 wedged catheter injections with iohexol induced VF within 28 sec (19 +/- 1 [mean +/- standard error of the mean]) despite pretreatment with antiarrhythmic drugs. Prior to VF, conduction was slowed and monophasic action potential duration lengthened in the contrast-medium-perfused myocardium, although no significant changes occurred in the control area. CONCLUSION: The combination of catheter wedging and long-lasting contrast medium injection has a high risk of causing VF. Although adding a small amount of electrolytes to nonionic contrast media can reduce the risk of VF, antiarrhythmic drug therapy may not have a protective effect. 相似文献
43.
TS Frank RE Bartos HK Haefner JA Roberts MD Wilson GP Hubbell 《Canadian Metallurgical Quarterly》1994,7(1):3-8
Eight anticonvulsant drugs-including clonazepam, diazepam and phenobarbital-were tested for their effects on GABA-stimulated chloride uptake in rat cerebral cortical microsacs (unfiltered synaptoneurosomes). "Mid" and "high" therapeutic concentrations were screened, and, if significant enhancement was found, full concentration-response tests were done. In the initial screens, enhancement of GABA-stimulated uptake was found only with phenobarbital, clonazepam and diazepam. In subsequent concentration-response tests, the effects of phenobarbital were found to occur throughout the range of normal, anticonvulsant concentrations, whereas the effects of clonazepam and diazepam were observed only above the concentrations normally used for the chronic control of seizures or anxiety. These data suggest that phenobarbital's anticonvulsant effects are mediated via the GABAA receptor complex, but that the low-dose effects of the benzodiazepines may be mediated via some other mechanism. 相似文献
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HK Kimelberg 《Canadian Metallurgical Quarterly》1998,19(1):27-34; discussion 37-8
47.
HK Parmentier G De Vries Reilingh MG Nieuwland 《Canadian Metallurgical Quarterly》1998,66(3-4):367-376
Mitogen-induced cutaneous hypersensitivity was evaluated in chickens selected for high and low antibody responses to SRBC, and in a random bred control line. Wing web swelling responses were found after subcutaneous administration of phytohemagglutinin (PHA), concanavalin A (Con A), pokeweed mitogen (PWM), and Escherichia coli lipopolysaccharide (LPS), respectively, in all three lines. All mitogens induced significant acute 4 h wing web swelling responses, followed by a significant (classical) late 24 h wing web swelling response. The 4 h responses were significantly lower in the L line, whereas a tendency for lower responses at 24 h in the L line was found as well. Immunohistochemical evaluation of the early and late wing web swelling responses revealed extravascular localisation of leukocytes at 24 h after sensitization with mitogens, which consisted of CD4+ cells, CD8+ cells, TCR-1+ cells, and heterophils, but no B cells, whereas the 4 h swelling response was primarily characterized by oedema. Cutaneous hypersensitivity either initiated by T-cell mitogens as well as B-cell mitogens may depend for an important part on the rapid induction of local homing of lymphocytes towards the sensitizing agent, which may be mediated by an acute local expression of molecules with chemo-attractive capacities. Interpretation of cellular immunity responses in vivo such as delayed-type hypersensitivity should therefore incorporate oedema-initiating characteristics of sensitizing agents. The relationship between the magnitude of cutaneous hypersensitivity to mitogens and selection for antibody responsiveness is discussed. 相似文献
48.
Expression/induction of the 72 and 60 kDa heat shock proteins (HSPS 72 and 60) in cultured human keratinocytes by high calcium was studied with immunofluorescent staining and the flow cytometric method. Normal human keratinocytes cultured in serum free, low calcium medium (Ca2+, 0.1 mM) at 3-passage weakly expressed HSP 60, but not HSP 72, as fine granules in the cytoplasm. HSP 72 was induced in the perinuclear cytosomal area and then in the nucleus after transferring the cells in high calcium medium (Ca2+, 1.8 mM). Whereas the nuclear accumulation began to decrease 24 h after the treatment, the perinuclear cytosomal staining continued. High calcium also augmented the expression of HSP 60 as coarse granules in the cytoplasm. Flow cytometric analyses quantitatively revealed the induction of HSP 72 and the upregulation of HSP 60 by high calcium treatment. Our results clearly demonstrated that extracellular calcium concentration modifies the level of expression of HSP 72 and 60 in normal human keratinocytes, indicating the importance of the careful attention to medium condition in evaluating the expression of HSPS 72 and 60 in cultured keratinocytes. 相似文献
49.
BACKGROUND AND OBJECTIVES: The para-Bombay phenotype has a relatively high frequency of about 1 in 8,000 Taiwanese. Studies were carried out on eight healthy and unrelated Taiwanese with the para-Bombay phenotype to cast light on its immunogenetic basis. MATERIALS AND METHODS: Blood and saliva samples were tested with standard hemagglutination techniques. Salivary ABH substances were determined by hemagglutination inhibition. PCR techniques were used to amplify the coding region of the H genes. RESULTS: Five different h alleles, designated as h1, h2, h3, h4 and h5, were identified in the Taiwanese with the para-Bombay phenotype. The h1 allele loses one of the three AG repeats located at the nucleotides 547-552 of the H gene, whereas two of the three T repeats located at the nucleotides 880-882 are deleted in the h2 allele. The h3 allele contains a C658 to T missense mutation, whereas two missense mutations, C35 to T and A980 to C were identified in the h4 allele. A T460 to C missense is present in the h5 allele. The h5 allele was identified in an individual whose red blood cells contain blood group A antigen but not H antigen, and thus may be considered a weak variant of the H gene. CONCLUSIONS: So far no biologic relevance of the H antigen has been discovered, and its deficiency does not seem to produce any deleterious effects. There may be better understanding of the evolutionary basis for the polymorphisms at these loci after systematic study of different ethnic populations. 相似文献
50.
D Busse FW Busch F Bohnenstengel M Eichelbaum P Fischer J Opalinska K Schumacher E Schweizer HK Kroemer 《Canadian Metallurgical Quarterly》1997,15(5):1885-1896
PURPOSE: The alkylating anticancer agent cyclophosphamide (CP) is a prodrug that undergoes a complex metabolism in humans producing both active and inactive metabolites. In parallel, unchanged CP is excreted via the kidneys. The aim of this study was to investigate the influence of dose escalation on CP pharmacokinetics and relative contribution of activating and inactivating elimination pathways. PATIENTS AND METHODS: Pharmacokinetics of CP were assessed in 12 patients with high-risk primary breast cancer who received an adjuvant chemotherapy regimen that included four courses of conventional-dose CP (500 mg/m2 over 1 hour every 3 weeks) followed by one final course of high-dose CP (100 mg/kg over 1 hour). Plasma concentrations of CP were analyzed by high-performance liquid chromatography (HPLC), 24-hour urinary concentrations of CP, and its inactive metabolites (carboxyphosphamide, dechloroethylcyclophosphamide [dechlorethylCP], ketocyclophosphamide [ketoCP]) were determined by 31-phosphorus-nuclear magnetic resonance (31P-NMR)-spectroscopy. RESULTS: There was no difference in dose-corrected area under the concentration-time curve (AUC) (216 v 223 [mumol.h/[mL.g]), elimination half-life (4.8 v 4.8 hours), systemic clearance (79 v 77 mL/min) and volume of distribution (0.49 v 0.45 L/kg) of CP between conventional- and high-dose therapy, respectively. However, during high-dose chemotherapy, we observed a significant increase in the renal clearance of CP (15 v 23 mL/min; P < .01) and in the formation clearance of carboxyphosphamide (7 v 12 mL/min; P < .05) and dechloroethylCP (3.2 v 4.2 mL/min; P < .05), whereas metabolic clearance to ketoCP remained unchanged (1.3 v 1.2 mL/min). Consequently, metabolic clearance to the remaining (reactive) metabolites decreased from 52 to 38 mL/min (P < .001). The relative contribution of the different elimination pathways to overall clearance of CP demonstrated wide interindividual variability. CONCLUSION: Overall pharmacokinetics of CP are apparently not affected during eightfold dose escalation. However, there is a shift in the relative contribution of different clearances to systemic CP clearance in favor of inactivating elimination pathways, thereby indicating saturation of bioactivating enzymes during dose escalation. Besides individual enzyme capacity, hydration and concomitant medication with dexamethasone modulated CP disposition. 相似文献