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51.
HM Chaung CH Hong CP Chiang SK Lin YS Kuo WH Lan CC Hsieh 《Canadian Metallurgical Quarterly》1996,95(7):545-550
This review reports the different genetic factors that have been identified either as risk factor for Alzheimer's disease (AD) or directly causing the disease. First are reviewed epidemiological data and biological mechanisms about the apoplipoprotein E gene allele epsilon 4 that is a major risk factor for Alzheimer's disease. The second part describes the mutations responsible for early-onset autosomal dominant AD found in three different genes. The gene located on chromosome 21 encodes the amyloid precusor protein (APP). The presenilin 1 and presenilin 2 genes, located on chromosome 14 and 1 respectively, encode not yet known membrane proteins. 相似文献
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54.
T De Brito CR Carneiro MC Nakhle DM Lima CP Abrantes-Lemos M Sandoval AM Silva 《Canadian Metallurgical Quarterly》1998,6(4):368-376
Gene therapy has the potential to provide cancer treatments based on novel mechanisms of action with potentially low toxicities. This therapy may provide more effective control of loco-regional recurrence in diseases such as non-small cell lung cancer (NSCLC), as well as systemic control of micrometastases. Despite current limitations, retroviral and adenoviral vectors can in certain circumstances provide an effective means of delivering therapeutic genes to tumour cells. Although multiple genes are involved in the process of carcinogenesis, mutations of the p53 gene are the most frequent abnormality identified in human tumours. Pre-clinical studies both in vitro and in vivo have shown that restoration of p53 function can induce apoptosis in cancer cells. Phase I clinical trials now show that p53 gene replacement therapy is feasible and safe using both retroviral and adenoviral vectors, and that it induces tumour regression in patients with advanced NSCLC and recurrent head and neck cancer. Other pre-clinical studies indicate that gene therapy may have useful synergy with cytotoxic and radiation therapy. This paper describes the different gene therapy strategies under investigation and the pre-clinical data that provides a rationale for the gene replacement approach, reviews clinical trial data and presents novel ideas for improving current vectors and gene delivery to tumours. 相似文献
55.
The aims of this study were to establish a working rabbit heart model of regional myocardial ischaemia in which electrophysiologic parameters and arrhythmogenesis could be correlated and to explore the mechanisms underlying the antiarrhythmic activity of lignocaine. Monophasic action-potential duration (MAPD90), effective refractory period (ERP), and conduction delay were measured at three ventricular sites in isolated hearts paced at 3.3 Hz. The hearts were treated before and throughout 30 min of ischaemia and 15 min of reperfusion with a vehicle or 20 microM lignocaine. In both groups, ischaemia produced a similar shortening in MAPD90. Lignocaine decreased ERP shortening during ischaemia from -56+/-4 to -32+/-6 ms. An ischaemia-induced increase in conduction delay was greater in the lignocaine than the control group (49+/-7 vs. 11+/-2 ms). Ischaemia-induced dispersion of repolarisation was reduced by lignocaine from 66+/-4 to 32+/-7 ms, and dispersion of refractoriness was decreased from 57+/-6 to 16+/-3 ms. Lignocaine decreased inducibility of ventricular fibrillation (VF) during ischaemia from 86 to 25%. We conclude that, in this model, the antiarrhythmic activity of lignocaine during regional ischaemia is associated with an increase in ischaemia-induced conduction delay and reduced dispersion of repolarisation and refractoriness. 相似文献
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FR Matuschka TW Schinkel B Klug A Spielman D Richter 《Canadian Metallurgical Quarterly》1998,64(8):3089-3091
To define conditions promoting inherited infection by Lyme disease spirochetes in Ixodes ticks, we variously infected ticks with Borrelia afzelii and examined their progenies by dark-field microscopy, immunofluorescence, PCR, and serial passage. No episode of inherited infection was evident, regardless of instar or gender infected or frequency of exposure. We suggest that these spirochetes rarely, if ever, are inherited by vector ticks. 相似文献
58.
SB Dennis VG Allen KE Saker JP Fontenot JY Ayad CP Brown 《Canadian Metallurgical Quarterly》1998,76(10):2687-2693
Poor performance of livestock that graze tall fescue (Festuca arundinacea Schreb.) has been associated with the endophyte fungus Neotyphodium coenophialum [Morgan-Jones and Gams] Glenn, Bacon, and Hanlin). Recent evidence suggests lowered Cu status and a depression of Cu-related immune function in steers that graze endophyte-infected (E+) tall fescue. Greenhouse and field studies investigated relationships between the endophyte and Cu concentrations in tall fescue. Seventeen infected 'Kenhy' clones were divided, and one plant of each pair was treated three times with Benomyl to remove the endophyte (E-). Plants were watered with nutrient solution in a greenhouse for 6 mo before sampling. Copper concentrations were greater (P < .001) in E- than in E+ clones (3.4 vs 2.8 microg/g; SE, .06). In the second greenhouse experiment, genetically similar E+ and E- 'Kentucky'-31 (KY-31) and 'Georgia Jessup' were grown from seed and fertilized with nutrient solution to produce mature plants. Copper concentrations were higher (P < .05) in E- than in E+ tall fescue (8.6 vs 7.6 microg/g; SE, .3). In a field plot experiment in Texas, E+ and E- KY-31 were grown with 0, 50, and 100% replacement of potential evapotranspiration. By September, Cu concentrations were higher (P < .05) in E- than in E+ tall fescue (7.3 vs 6.6 microg/g; SE, .2). In pasture experiments, KY-31 E+ (> 70% infection level) and E- (< 5% infection level) tall fescue were grown in Virginia at two locations with three rates of N fertilizer. Copper concentrations were higher (P < .05) in E- than in E+ tall fescue (4.8 vs 4.5 microg/g; SE, .1) and increased (P < .01) linearly in response to N. Our data demonstrate that the presence of the endophyte is associated with lower Cu concentrations in tall fescue, which may contribute to lowered Cu status in animals and thus contribute to the etiology of fescue toxicity. 相似文献
59.
Kalinnik Natalia Kiesel Robert Rauber Thomas Richter Marcel Rünger Gudula 《The Journal of supercomputing》2021,77(4):3484-3515
The Journal of Supercomputing - Scientific application codes are often long-running time- and energy-consuming parallel codes, and the tuning of these methods towards the characteristics of a... 相似文献
60.
Otto Richter Thomas Schmidt Hand Büning-Pfaue und Dietrich Reinhardt 《Zeitschrift für Lebensmitteluntersuchung und -Forschung A》1988,187(2):130-136
Zusammenfassung Es werden pharmakokinetische Modelle angegeben, um den Konzentrationsverlauf von Arzneimittelrückständen im Menschen zu berechnen, die mit der Nahrung aufgenommen werden. Dabei lassen sich zwei Kompartimentmodelle für die Kinetik in der Nahrung und im Menschen koppeln: Das erste System liefert die Anfangswerte (bzw. eine Folge von Anfangswerten) für das zweite System. Das Modell wird auf die Übertragung von Chloramphenicol durch Speisefische auf den Menschen und auf die Übertragung von Theophyin durch die Muttermilch auf gestillte Säuglinge angewendet. Durch Einführung einer günstigsten und ungünstigsten Parameterkombination werden Grenzverläufe für die Blutspiegel berechnet, die als Grundlage einer Rückstandsbewertung dienen können.
Residues of active substances following the consumption of contaminated food —Status report on the evaluation of residues based on two drugs
Summary Pharmacokinetic models are presented for the computation of time courses of blood levels of drugs in man following the consumption of contaminated food. Mathematically, two linear systems of differential equations are set up for the donor organism (e.g., trout) and for the recipient, (e.g., man), where the first system generates the initial conditions for the second. Models of this kind are applied to the transfer of chloramphenicol to man via carp and trout (which had previously been administered this drug) and to the transfer of theophylline to infants via breast milk. Limiting concentration profiles are computed by constructing the most favourable and most adverse combinations of parameters with respect to drug elimination in both the donor and recipient organism.相似文献