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Y Okada M Tsukatani H Taguchi T Yokoi SD Bryant LH Lazarus 《Canadian Metallurgical Quarterly》1998,46(9):1374-1382
An amino group was introduced to the 3 or 6 position of a pyrazinone ring by cyclization of dipeptidyl chloromethyl ketones. Boc-Tyr-OH was coupled with the amino function, followed by removal of the Boc group to give pyrazinone ring-containing tyrosine derivatives. Of the various tyrosine derivatives prepared, 5-methyl-6-beta-phenethyl-3-tyrosylaminobutyl-2(1H)-pyrazinone exhibited strong binding to the mu-opioid receptor with a Ki value of 55.8 nM and to the delta-opioid receptor with a Ki value of 2165 nM and with a Ki mu/Ki delta value of 0.026. 相似文献
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Y Hiramatsu N Gikakis JH Gorman MM Khan CE Hack HT Velthuis L Sun C Marcinkiewicz AK Rao S Niewiarowski RW Colman LH Edmunds HL Anderson 《Canadian Metallurgical Quarterly》1997,130(4):412-420
Objective investigation of new inhibitors of blood protein or cellular systems that are activated during cardiopulmonary bypass (CPB) is impeded by the absence of a satisfactory animal model. Because most baboon hematologic proteins immunologically cross-react with those used for human assays, we developed a robust, reusable baboon model of CPB. Blood samples were obtained from adult baboons at six time intervals before, during, and after 60 minutes of partial CPB at 37 degrees C with peripheral cannulas. Both membrane (n = 7) and bubble oxygenators (n = 7) were investigated. We measured platelet and white blood cell counts; platelet response to adenosine diphosphate and release of beta-thromboglobulin; fibrinopeptide A, prothrombin fragment F1.2, thrombin-antithrombin complex, D-dimer, and plasmin-antiplasmin complex; activated complement (C3b/c and C4b/c); elastase-alpha1 proteinase inhibitor complex; and bleeding times. Adherent glycoprotein IIIa antigen in Triton X-100 washes of the perfusion circuit was also measured. Markers of baboon platelet, complement, and neutrophil activation and thrombosis significantly increased during CPB with bubble oxygenator systems but did not change appreciably in membrane oxygenator circuits. Markers of fibrinolysis, D-dimer, and plasmin-antiplasmin complex did not change with either oxygenator. The baboon model of CPB, when a bubble oxygenator is used, is a robust, reusable animal model for evaluating inhibitors of platelet, complement, and neutrophil activation and thrombosis during and after CPB. 相似文献
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A high glycogen level may be beneficial to the ischemic heart by providing glycolytic ATP or detrimental by increasing intracellular lactate and protons. To determine the effect of high glycogen on the ischemic myocardium, the glycogen content of Langendorff-perfused rat hearts was either depleted or elevated before 32 minutes of low-flow (0.5 mL/min) ischemia with Krebs-Henseleit buffer with or without 11 mmol/L glucose, followed by 32 minutes of reperfusion with buffer containing 11 mmol/L glucose. 31P nuclear magnetic resonance spectra were acquired sequentially throughout. Further experiments involved early reperfusion or the addition of HOE 694, a Na+-H+ exchange inhibitor, during reperfusion. When glucose was supplied throughout ischemia, no ischemic contracture occurred, and postischemic recovery of contractile function was highest, at 88% of preischemic function. In the absence of glucose, normal-glycogen hearts underwent ischemic contracture at 5 minutes, had an end-ischemic pH of 6.87, and recovered to 54%, whereas in high-glycogen hearts, contracture was delayed to 13 minutes, the end-ischemic pH was 6.61, and functional recovery decreased to 13%. Contracture onset coincided with the decrease in glycolysis, which occurred as glycogen became fully depleted. Functional recovery in the high-glycogen hearts increased to 89% when reperfused before contracture and to 56% when reperfused in the presence of HOE 694. Thus, during brief ischemia in the high-glycogen hearts, ischemic glycogen depletion and contracture were avoided, and the hearts were protected from injury. In contrast, during prolonged ischemia in the high-glycogen hearts, glycogen became fully depleted, and myocardial injury occurred; the injury was exacerbated by the lower ischemia pH in these hearts, leading to increased Na+-H+ exchange during reperfusion. The contradictory findings of past studies concerning the effect of high glycogen on the ischemic myocardium may thus be due to differences in the extent of glycogen depletion during ischemia. 相似文献
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LE Hann GI Getrajdman KT Brown AM Bach JB Teitcher Y Fong LH Blumgart 《Canadian Metallurgical Quarterly》1996,167(4):1017-1021
OBJECTIVE: This study was performed to evaluate the association between hepatic lobar atrophy, bile duct obstruction, and portal vein obstruction. MATERIALS AND METHODS: Thirty cases of hepatic lobar atrophy identified on angiography with CT during arterial portography from August 1992 to March 1995 were retrospectively reviewed by two independent observers. Cases were evaluated for vascular patency and bile duct obstruction. Malignant diagnoses were present in 28 of 30 patients. RESULTS: Twenty-two patients (73%) had atrophy in the left lobe and eight patients (27%) had right lobar atrophy. Portal vein obstruction was unilateral and confined to the atrophic lobe in 26 patients (87%). In contrast, bile duct obstruction was bilateral in 23 patients (77%) and in only four patients (13%) was it isolated to the atrophic lobe. The correlation between atrophy and portal vein obstruction was significant, with 90% sensitivity, 97% specificity, and 96% positive predictive value (p < .00001). For the correlation between atrophy and biliary obstruction, the sensitivity of angiography with CT during arterial portography was 90%, specificity was 23%, and positive predictive value was 54% (p = .17). CONCLUSION: Hepatic lobar atrophy usually occurs in the setting of combined biliary and portal vein obstruction. A significant correlation exists between hepatic lobar atrophy and ipsilateral portal vein obstruction. 相似文献