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961.
M Portero-Otín R Pamplona MJ Bellmunt M Bergua RH Nagaraj J Prat 《Canadian Metallurgical Quarterly》1997,60(4-5):279-287
The presence of pyrraline, a non-oxidative glucose-derived Maillard reaction product in plasma proteins has been established previously. In this study we have investigated the presence of pyrraline in human urine to determine whether pyrraline-containing proteins are metabolized or selectively retained. Pyrraline was detected by means of HPLC, and its presence was confirmed by UV and electrospray-mass spectrometry. The quantification of pyrraline in urine from healthy individuals showed 1.21 +/- 0.4 micrograms/mg creatinine. In urine from diabetic patients, pyrraline levels varied considerably, although the mean level was higher than in healthy subjects (1.37 +/- 0.6 micrograms/mg creatinine). These data further support the presence of a catabolic pathway for advanced non-oxidative Maillard reaction products in vivo and suggest their role in the pathogenesis of diabetes. 相似文献
962.
A replication-defective vector based on human immunodeficiency virus (HIV) was evaluated for gene transfer directed to the lung. The tropism of this vector has been expanded through the incorporation of the vesticular stomatitis virus G protein into its envelope. The HIV vector effectively transduced nondividing airway epithelial cells in vitro whereas a murine-based retroviral vector did not. Experiments in a human bronchial xenograft model demonstrated high-level gene transduction with a cystic fibrosis transmembrane conductance regulator (CFTR) HIV vector into undifferentiated, cystic fibrosis (CF)-derived cells of the xenograft. CFTR expression was stable and capable of functional correction of the CF defect after the graft matured. The HIV vector did not effectively transduce cells of the xenograft when instilled after the epithelium had differentiated. This block to transduction appears to be at the level of entry, although post entry restrictions cannot be ruled out. Further development of this vector system for CF gene therapy should focus on a better understanding of potential entry and post entry blocks. 相似文献
963.
MJ Bruno JJ Borm FJ Hoek B Delzenne AF Hofmann JJ de Goeij EA van Royen TM van Gulik LT de Wit DJ Gouma DJ van Leeuwen GN Tytgat 《Canadian Metallurgical Quarterly》1997,84(7):952-956
BACKGROUND: A comparative study was performed between patients with exocrine pancreatic insufficiency after conventional pancreatoduodenectomy (Whipple's procedure) and pylorus-preserving pancreatoduodenectomy (PPPD). In these patients the pharmacodynamics of 2-mm enteric-coated pancreatin microspheres (ECPMs) and their gastric transit time in relation to that of a solid meal were investigated. The efficacy of ECPM preparations may differ after Whipple's procedure compared with PPPD, because the latter procedure does not include gastrectomy. METHODS: Gastric transit was assessed by double-isotope scintigraphy. A pancake meal was labelled with 99mTc. ECPMs were cold-labelled with 170Er and neutron activated shortly before ingestion to enable imaging with a gamma camera. Intraluminal pancreatic enzyme activity was assessed during a 6-h period with two indirect tests: the cholesteryl [14C]octanoate breath test and the N-benzoyl-L-tyrosyl-p-aminobenzoic acid-p-aminosalicylic acid (NBT-PABA-PAS) test. RESULTS: In patients who had Whipple's procedure, the gastric transit time of ECPMs and of the pancake meal was not significantly different. The outcome of the indirect pancreatic function tests during enzyme supplementation was comparable, and not significantly different, from that in healthy volunteers. In patients who had PPPD, however, the gastric transit time of microspheres was greatly delayed compared with that of the pancake meal (P < 0.05). Improvement in the outcome of the indirect pancreatic function tests during enzyme supplementation was much less and remained well below that of healthy volunteers (P < 0.05). CONCLUSION: In cases of exocrine pancreatic insufficiency after Whipple's procedure, 2-mm ECPM treatment adequately restores pancreatic enzyme activity. Following PPPD, however, ECPM treatment is often ineffective because the microspheres are retained in the stomach. In these patients, use of conventional powdered pancreatin enzyme preparations may improve the efficacy of treatment. 相似文献
964.
HE Greenberg MJ England ET Hellriegel TD Bjornsson 《Canadian Metallurgical Quarterly》1997,37(6):480-485
The time of peak concentration after administration of oral drug is an often quoted and used pharmacokinetic parameter. It is not well appreciated, however, that the peak times after a single dose and a dose at steady state during a multiple administration regimen can differ significantly. This article derives the mathematical relationships that determine how a peak time at steady state differs from that after a single or first dose. These relationships are then evaluated using three different approaches: 1) graphic simulations of time courses of drug concentration for three hypothetical drugs; 2) comparisons of predicted and observed peak times using examples from the literature; and 3) comparisons of predicted and simulated peak times based on different sampling schedules for three hypothetical drugs. The key finding is that peak times after a dose at steady state can occur considerably earlier after administration than after a single dose. However, the manner by which peak times are usually determined, that is, the sampling time corresponding to the highest measured drug concentration, imposes significant limitations on the usefulness of this parameter. 相似文献
965.
VM Heinrichs MJ Kemper M Burdelski D Kluth DE Mueller-Wiefel H Schaefer M Luebeck 《Canadian Metallurgical Quarterly》1997,38(5):818-820
Disseminated islands of gastric mucosa are very rare in the small intestine. The secretion of hydrochloric acid can lead to ulceration which results in gastrointestinal bleeding. It is often difficult to localize the focus in case of gastrointestinal blood loss especially in the small bowel. Technetium-99m-pertechnetate scintigraphy may be a helpful tool in detecting ectopic gastric mucosa. We report a case of a 21-mo-old boy with recurrent gastrointestinal bleeding. By using pertechnetate scintigraphy, extensive tracer accumulation in the jejunum and proximal ileum was detected. Histologically, multiple islands of ectopic gastric mucosa were found in about 50 excited mucosal and transmural biopsies. The unusual finding of disseminated accumulation of 99mTc-pertechnetate in the small intestine was the diagnostic clue for such a rare disease. 相似文献
966.
In the course of biotransformation reactions catalyzed both by cytochrome P450 and by conjugating enzymes, drug-derived reactive metabolites and active oxygen species can appear that may escape the detoxification process, initiating radical chain reactions (e.g., lipid peroxidation), covalently binding to macromolecules (proteins, DNA), or impairing the energetic balance of cells. This is usually followed by alterations of ion homeostasis that precede irreversible biochemical changes and cell death. There are, however, cellular mechanisms of defense that prevent, or repair, the damage caused by these reactive intermediates. Ultimately it is the balance between bioactivation, detoxification, and defense mechanisms that determines whether a compound will or will not elicit a toxic effect. Cultures of hepatocytes, including those of human origin, can be used to elucidate the mechanisms of drug toxicity. This is illustrated in the study of the mechanism of hepatotoxicity by diclofenac. Much less cytotoxicity is observed in nonmetabolizing hepatomas than in hepatocytes. The observed cell dysfunction parallels the biotransformation of the drug, and particularly the formation of the minor metabolite N,5-dihydroxydiclofenac by hepatocytes. This compound is able to inhibit mitochondrial ATP synthesis in hepatocytes. 相似文献
967.
Receptor binding studies and electrophysiological studies demonstrated the existence of at least two kappa opioid receptors, which have been designated kappa-1 and kappa-2. Several agonists and antagonists are selective for the kappa-1 receptor whereas no known ligands are selective for the kappa-2 receptor. In this study, the kappa opioid GR89,696 was tested in the guinea pig hippocampal slice preparation for kappa-1 versus kappa-2 activity. The perforant path-evoked population spike in the dentate was use to evaluate activity at the kappa-1 receptor, and the Schaffer collateral-evoked N-methyl-D-aspartate (NMDA) receptor-mediated synaptic current in CA3 pyramidal cells was used to measure kappa-2 receptor activation. GR89,696 had no effect on the perforant path-evoked dentate population spike; however, it did reverse the effects of the selective kappa-1 agonist U69,593 when co-perfused over the slices. In the CA3, GR89,696 inhibited the NMDA receptor-mediated synaptic current. The inhibition was antagonized by naloxone. The EC50 for GR89,696 on the NMDA current was 41.7 nM (95% CL, 7.0-248 nM). These findings indicate that GR89,696 is an agonist for kappa-2 opioid receptors and an antagonist at kappa-1 receptors in the guinea pig hippocampus. 相似文献
968.
969.
MJ Barry FJ Fowler L Bin JC Pitts CJ Harris AG Mulley 《Canadian Metallurgical Quarterly》1997,157(1):10-4; discussion 14-5
PURPOSE: We defined outcomes for men with a clinical diagnosis of benign prostatic hyperplasia. MATERIALS AND METHODS: We followed for 4 years 500 candidates for elective prostatectomy treated nonoperatively in 5 North American urology practices. RESULTS: There were 371 survivors with complete data at 4 years. Of 60 men with mild, 245 with moderate and 66 with severe baseline symptoms 10, 24 and 39%, respectively, had undergone surgery; 27, 31 and 27%, respectively, were on pharmacological therapy, and 63, 45 and 33%, respectively, were off active treatment at 4 years. Mild or moderate symptoms were noted at 4 years in 83, 59 and 23% of the patients, respectively, while 17, 41 and 77%, respectively, had severe symptoms or had undergone surgery. CONCLUSIONS: Outcomes for men with a clinical diagnosis of benign prostatic hyperplasia depend on initial symptom severity. However, the course of symptoms also varies among patients even with the same initial symptom severity. 相似文献
970.
P Lebrun MH Antoine R Ouedraogo B Pirotte A Herchuelz KE Cosgrove C Kane MJ Dunne 《Canadian Metallurgical Quarterly》1997,40(12):1403-1410
Radioisotopic and electrophysiological techniques were used to assess the effects of verapamil, a phenylalkylamine Ca2+ channel blocker, on K+ permeability of insulin-secreting cells. Verapamil provoked a concentration-dependent inhibition of 86Rb (42K substitute) outflow from prelabelled and perifused rat pancreatic islets. This property appears to be inherent to the phenylalkylamine Ca2+ channel blockers since gallopamil, a methoxyderivative of verapamil, but not nifedipine, a 1,4-dihydropyridine Ca2+ channel blocker, inhibited 86Rb outflow. The experimental data further revealed that verapamil interacted with a Ca2+-independent, glucose- and glibenclamide-sensitive modality of 86Rb extrusion. Moreover, verapamil prevented the increase in 86Rb outflow brought about by BPDZ 44; a potent activator of the ATP-sensitive K+ channel. Single-channel current recordings by the patch clamp technique confirmed that verapamil elicited a dose-dependent inhibition of the ATP-dependent K+ channel. Lastly, under experimental conditions in which verapamil clearly inhibited the ATP-sensitive K+ channels, the drug did not affect 45Ca outflow, the cytosolic free Ca2+ concentration or insulin release. It is concluded that the Ca2+ entry blocker verapamil inhibits ATP-sensitive K+ channels in pancreatic beta cells. This effect was not associated with stimulation of insulin release. 相似文献