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WJ Ellis RL Vessella JL Noteboom PH Lange RL Wolfert HG Rittenhouse 《Canadian Metallurgical Quarterly》1997,50(4):573-579
OBJECTIVES: Treatment failure after radical prostatectomy is most commonly heralded by an increase in serum prostate-specific antigen (PSA) to detectable levels. We evaluated the clinical utility of an ultrasensitive chemiluminescent PSA assay. METHODS: We evaluated the assay in banked sera obtained from 170 men after radical prostatectomy. Controls consisted of 142 females, 29 men who had undergone cystoprostatectomy without evidence of prostate cancer, and 25 men without evidence of recurrent disease at least 5 years after prostatectomy for organ-confined disease. Lead time to diagnosis of recurrence was based on comparisons with the IMx or Tandem E assays using a cutoff of 0.1 ng/mL (100 pg/mL). RESULTS: The biologic level of detection of this assay is 8 pg/mL. Serum PSA levels were undetectable in 82.4% of females, 86.2% of the cystoprostatectomy patients, and 96% of the radical prostatectomy controls. After radical prostatectomy, PSA levels were undetectable at last check in 104 of 168 (61.9%) men. In the 24 men with prostate cancer recurrence, the enhanced sensitivity of 8 pg/mL provided a mean lead time based on conservative calculations of 12.7 to 22.5 months over conventional assays. Thirty-four of the 41 men with detectable PSA levels and no evidence of disease recurrence had PSA levels of 30 pg/mL or less. CONCLUSIONS: PSA levels are undetectable in most men who do not have recurrence of disease after radical prostatectomy. Low but detectable serum PSA levels less than or equal to 30 pg/mL can be produced by nonmalignant sources of PSA. PSA assays with enhanced sensitivity can detect recurrent prostate cancer with significant lead time over conventional assays. 相似文献
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AC Egberts AW Lenderink FH de Koning HG Leufkens 《Canadian Metallurgical Quarterly》1997,17(3):149-155
OBJECTIVE: Trifluoromethane and CO are produced simultaneously during the breakdown of isoflurane and desflurane by dry CO2 absorbents. Trifluoromethane interferes with anesthetic agent monitoring, and the interference can be used as a marker to indicate anesthetic breakdown with CO production. This study tests representative types of gas monitors to determine their ability to provide a clinically useful warning of CO production in circle breathing systems. METHODS: Isoflurane and desflurane were reacted with dry Baralyme at 45 degrees C. Standardized samples of breakdown products were created from mixtures of reacted and unreacted gases to simulate the partial degrees of reaction which might result during clinical episodes of anesthetic breakdown using 1% or 2% isoflurane and 6% or 12% desflurane. These mixtures were measured by the monitors tested, and the indication of the wrong agent or a mixture of agents due to the presence of trifluoromethane was recorded and related to the CO concentration in the gas mixtures. RESULTS: When presented with trifluoromethane from anesthetic breakdown, monochromatic infrared monitors displayed inappropriately large amounts of isoflurane or desflurane. Agent identifying infrared and Raman scattering monitors varied in their sensitivity to trifluoromethane. Mass spectrometers measuring enflurane at mass to charge = 69 were most sensitive to trifluoromethane. CONCLUSION: Monochromatic infrared monitors were unable to indicate anesthetic breakdown via interference by trifluoromethane, but did indicate falsely elevated anesthetic concentrations. Agent identifying infrared and Raman monitors provided warning of desflurane breakdown via the interference of trifluoromethane by displaying the wrong agent or mixed agents, but may not be sensitive enough to warn of isoflurane breakdown Some mass spectrometers provided the most sensitive warnings to anesthetic breakdown via trifluoromethane, but additional data processing by some patients monitor units reduced their overall effectiveness. 相似文献
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J Konvalinka J Litera J Weber J Vondrásek M Hradílek M Soucek I Pichová P Majer P Strop J Sedlácek AM Heuser H Kottler HG Kr?usslich 《Canadian Metallurgical Quarterly》1997,250(2):559-566
Human immunodeficiency virus (HIV) proteinase (PR) represents an important target for antiviral chemotherapy. We present an analysis of inhibitory activities of a series of pseudopeptide inhibitors of HIV-1 PR. All inhibitors were N-protected tetrapeptides with the scissile bond replaced by a nonhydrolysable hydroxyethylene or hydroxyethylamine isostere. To elucidate subtle structural requirements of the PR binding cleft, we synthesised inhibitors with four combinations of configurations at the asymmetric carbons of the isostere. Compounds were tested in vitro using purified recombinant enzyme and a chromogenic peptide substrate. The differences in inhibition constants between individual diastereoisomers reached three orders of magnitude. The most active hydroxyethylene-containing inhibitor possessed the 2R,4S,5S configuration at the isostere. Inhibitor activity was also tested in mammalian cell culture by analysing reduction of viral polyprotein processing and virus infectivity. The results obtained in tissue culture were generally in agreement with the in vitro data, giving a similar order of potency for the individual diastereoisomers. The most active compounds completely blocked production of infectious virus. A simulation method for interaction was employed to build a model of the inhibitors in the PR active site, to identify the interactions responsible for the differences in activities of individual stereoisomers, and to estimate the relative contribution of individual structural features to the overall inhibitory activity. 相似文献
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The lobula giant motion detector (LGMD) in the locust visual system is a wide-field, motion-sensitive neuron that responds vigorously to objects approaching the animal on a collision course. We investigated the computation performed by LGMD when it responds to approaching objects by recording the activity of its postsynaptic target, the descending contralateral motion detector (DCMD). In each animal, peak DCMD activity occurred a fixed delay delta (15 = delta = 35 msec) after the approaching object had reached a specific angular threshold thetathres on the retina (15 degrees = thetathres = 40 degrees). thetathres was independent of the size or velocity of the approaching object. This angular threshold computation was quite accurate: the error of LGMD and DCMD in estimating thetathres (3.1-11.9 degrees) corresponds to the angular separation between two and six ommatidia at each edge of the expanding object on the locust retina. It was also resistant to large amplitude changes in background luminosity, contrast, and body temperature. Using several experimentally derived assumptions, the firing rate of LGMD and DCMD could be shown to depend on the product psi(t - delta). e-alphatheta(t-delta), where theta(t) is the angular size subtended by the object during approach, psi(t) is the angular edge velocity of the object and the constant, and alpha is related to the angular threshold size [alpha = 1/tan(thetathres/2)]. Because LGMD appears to receive distinct input projections, respectively motion- and size-sensitive, this result suggests that a multiplication operation is implemented by LGMD. Thus, LGMD might be an ideal model to investigate the biophysical implementation of a multiplication operation by single neurons. 相似文献