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81.
PA Burghaus BT Wellde T Hall RL Richards AF Egan EM Riley WR Ballou AA Holder 《Canadian Metallurgical Quarterly》1996,64(9):3614-3619
Merozoite surface protein 1 (MSP-1) of Plasmodium falciparum is an antimalarial vaccine candidate. The highly conserved 19-kDa C-terminal processing fragment of MSP-1 (MSP-1(19)) is of particular interest since it contains epitopes recognized by monoclonal antibodies which inhibit the invasion of erythrocytes in vitro. The presence of naturally acquired anti-MSP-1(19) antibodies in individuals exposed to malaria has been correlated with reduced morbidity, and immunization with an equivalent recombinant P. yoelii antigen induces substantial protection against this parasite in mice. We have expressed P. falciparum MSP-1(19) in Escherichia coli as a correctly folded protein and immunized Aotus nancymai monkeys by using the protein incorporated into liposomes and adsorbed to alum. After vaccination, the sera from these animals contained anti-MSP-1(19) antibodies, some of which competed for binding to MSP-1(19) with monoclonal antibodies that inhibit parasite invasion of erythrocytes in vitro. However, after challenge with either a homologous or a heterologous strain of parasite, all animals became parasitemic and required treatment. The immunization did not induce protection in this animal model. 相似文献
82.
BT Hill SA Shellard AM Fichtinger-Schepman HJ Schmoll A Harstrick 《Canadian Metallurgical Quarterly》1994,5(3):321-328
Mechanisms of cisplatin resistance have been studied in two independently-selected sublines expressing clinically-relevant levels of resistance (3-fold) and established from a primary testicular teratoma obtained from previously untreated patients. Resistance was not associated with any significant modification in cellular uptake of cisplatin, in total glutathione levels or associated enzyme activities. However, immunochemical quantitation of specific platinum-DNA adduct formation and removal revealed that both resistant sublines were more proficient in repairing certain adducts than their generally repair deficient respective parental lines. SUSA/CP+ cells were more efficient in removing the intrastrand adducts in the sequence Pt-AG and the bi-functional Pt-(GMP)2 lesions, as well as DNA-DNA interstrand cross-links, whilst H12.1/DDP cells were highly proficient in removing the major Pt-GG intrastrand adducts. 相似文献
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MJ Hasbani KL Hyrc BT Faddis C Romano MP Goldberg 《Canadian Metallurgical Quarterly》1998,154(1):241-258
The postsynaptic neuronal dendrite is selectively vulnerable to hypoxic-ischemic brain injury and glutamate receptor overactivation. We explored the glutamate receptor pharmacology and ionic basis of rapid, reversible alterations in dendritic shape which occur in cultured neurons exposed to glutamate. Dendrite morphology was assessed with the fluorescent membrane tracer, DiI, or immunofluorescence labeling of the somatodendritic protein, MAP2. Cortical cultures derived from 15-day-old mouse embryos underwent segmental dendritic beading when exposed to NMDA, AMPA, or kainate, but not to metabotropic glutamate receptor agonists. Varicosity formation in response to NMDA or kainate application was substantially attenuated in reduced sodium buffer (substituted with N-methyl-D-glucamine). Furthermore, veratridine-induced sodium entry mimicked excitotoxic alterations in dendrites and additionally caused varicosity formation in axons. Solutions deficient in chloride (substituted with Na methylsulfate) and antagonists of chloride-permeable GABA/glycine receptors reduced NMDA- or kainate-induced varicosity formation. An increase in dendrite volume was observed as varicosities formed, and varicosity formation was attenuated in sucrose-supplemented hypertonic media. Despite marked structural changes affecting virtually all neurons, dendrite shape returned to normal within 2 h of terminating glutamate receptor agonist application. Neurons exposed to kainate recovered more rapidly than those exposed to NMDA, and neurons exposed to NMDA in calcium-free buffer recovered more rapidly than cells treated with NMDA in normal buffer. While sodium, chloride, and water entry contribute to excitotoxic dendritic injury acutely, calcium entry through NMDA receptors results in lasting structural changes in damaged dendrites. 相似文献
85.
JW Ely KS Berbaum GR Bergus BH Thompson BT Levy MA Graber ER Evans DA Bedell DS Fick 《Canadian Metallurgical Quarterly》1996,43(3):242-248
Percutaneous cardiopulmonary assist devices (PCPS) have become available in interventional cardiology within recent years. These tools offer the opportunity of performing percutaneous transluminal coronary angioplasty (PTCA) in high-risk patients characterized by significant stenoses of several coronary arteries and a poor left ventricular function. It is unclear for which patients PCPS are necessary and which patients will profit by PTCA as compared to coronary artery bypass grafting (CABG). Therefore, the anticipated risk of CABG and of PTCA without assist devices was calculated according to risk scores and compared with our results of assisted PTCA. In addition the long-term survival rate was investigated. In 35 patients (mean 65.5 years of age, 12 females, 23 males), we performed PTCA concomitant with the use of cardiac assist devices. The indications for the use of a cardiac assist device were severely impaired LV function (EF 30% +/- 8.9%) in combination with significant coronary artery disease (2.7 +/- 0.3 vessels) and a significant supply area of the vessel to be dilated. In 6 patients, PCPS was started before coronary angioplasty because of hemodynamic instability. In 21 cases, PCPS was on a standby basis without being connected to the patient's circulation. In 8 patients, a left heart assist device, the 14F-Hemopump, was inserted percutaneously. The patients were analyzed using risk scores of angioplasty and of coronary bypass graft surgery. The calculated risk of hemodynamic compromise during PTCA according to the risk scores was more than 50%. The anticipated risk of a fatal outcome following CABG would have been 19.8%. PTCA was performed on an average of 2.0 coronary arteries per patient and was successful in 85%. We observed a decline in angina pectoris classification (CCS) from 3.5 to 1.6. An average reduction of 1.1 NYHA class was achieved. The in-hospital mortality was 8.6% (3 patients: 1 x sepsis, 1 x early reocclusion, 1 x cerebral embolism). At 24 months follow-up, a re-PTCA was necessary in four cases because of restenosis. In the remainder, NYHA and CCS class were stable during the follow-up period. An additional five patients died during the first year and two patients in the second year. We conclude that PTCA with the use of a cardiac assist device shows favorable short-term results in a subset of patients with extended coronary artery disease and severely impaired LV function who are not suitable for nonsupported PTCA or CABG due to their risk profile. However, the long term results are not satisfying and stress the need for complete revascularisation with CABG once the patient's condition is stabilized by means of supported PTCA. 相似文献
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Delta-THC (10 mg/kg, i.p.) administered to mice immediately after withdrawal from a 3-day exposure to ethanol vapor was found to intensify withdrawal reactions. No effect was seen when delta-THC was administered chronically during the exposure to ethanol. 相似文献
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