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61.
1. The excretion and metabolism of N-[2-(3,4-dimethoxyphenyl)ethyl]-5-methoxy-N,alpha-dimethyl-2-(phenyl ethynyl) benzenepropanamine (RWJ-26240) in the Wistar rat has been investigated after a single oral dose of 14C-RWJ-26240 (50 mg/kg free base). 2. Plasma samples were obtained for 24 h after dosing and urine and faecal samples were collected over 8 days, and they accounted for 0.9 and 96% of the dose, respectively. 3. Representative samples of plasma, urine and faecal samples were purified for metabolite isolation and identification using HPLC, tlc, mass spectra (CI and EI), 1H-NMR and derivatization. 4. Unchanged RWJ-26240 plus 11 metabolites were identified and accounted for > 80% of the sample radioactivity. 5. Four metabolic pathways for RWJ-26240 are proposed; namely (1) N-demethylation, (2) O-demethylation, (3) phenyl hydroxylation and (4) N-dealkylation. Pathways 1-3 appeared to be quantitatively more important. 相似文献
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63.
PURPOSE: Renal osteosarcoma may arise as a metastasis from a primary bone osteosarcoma or as a primary renal tumor. Metastatic renal osteosarcoma has been found at autopsy in approximately 10% of patients who die of this disease. PATIENT AND METHODS: A case report of a young Chinese patient presenting with acute onset of renal infarction and hemorrhage from a renal metastasis of osteosarcoma is presented, as well as a review of the literature. RESULTS: Some patients with solitary renal metastatic osteosarcoma may have long-term disease-free survival after nephrectomy. Early diagnosis and thus increased awareness of this condition is important. 相似文献
64.
The cornea of the toad, Bufo marinus, actively transports chloride from the endothelial to the epithelial surface. This transport process has been related to the maintenance of the normal transparency of the cornea. Ion transport, as evidenced by the short-circuit current (SCC), is markedly stimulated by physiologic concentrations of ascorbic acid. Measurement of the unidirectional fluxes of 36Cl and 22Na shows that the increase in SCC is due primarily to a stimulation of the active transport of chloride. 相似文献
65.
Albino Holtzman, albino Wistar and hooded HS rats were injected fortnightly for 14 weeks with human glomerular basement membrane (GBM) emulsified in Freund's complete adjuvant. Half of the rats were pretreated with Freund's complete adjuvant and some were unilaterally nephrectomized. Anti-GBM antibody glomerulonephritis, characterized by proteinuria (greater than 100 mg/16 h) and a diffuse linear deposition of host immunoglobulin along the glomerular basement membrane, was first detected in Holtzman rats 4 weeks after treatment with GBM had begun, and had developed in 69% of these rats by 15 weeks. In contrast, none of the similarly treated Wistar or HS rats became proteinuric at any time, although a few showed weak glomerular fluorescence at the end of the experiment. Thus Holtzman rats are susceptible, and HS and Wistar rats are resistant to experimental anti-GBM antibody glomerulonephritis. Pretreatment with Freund's complete adjuvant apparently shortened the induction period of the experimental disease in the Holtzman rats whereas unilateral nephrectomy appeared to decrease their susceptibility to it. 相似文献
66.
Yeast-phase cells of Histoplasma capsulatum were challenged with amphotericin B, and membrane perturbation was monitored by K+ efflux. Suspensions of washed cells readily absorbed about 1.12 microgram of amphotericin B per mg (dry weight) and further nonspecific sites were also apparent. The dose-response curve for initial rate of K+ efflux was sigmoidal within the range 0.1 to 1.0 microgram of amphotericin B per ml. A fungistatic concentration of amphotericin B (0.3 microgram/ml) evoked an efflux of 85 to 90% K+ from the cells within 15 min, but cell viability decreased only 13% (yeast phase) or 33% (transformed to mycelial units). Ultrastructural changes in treated cells were detected within 5 min, and the hallmark was expansion of vacuoles during the 1-h monitoring period. In contradistinction to a previous report, the appearance of the protoplasmic membrane was not altered by fungistatic concentration. When treated cells were returned to a fresh growth medium, there was a pronounced lag (20 h). During this apparent recovery phase, the large vacuoles fragmented and returned to normal size. It is proposed that vacuoles of H. capsulatum act as a spatial buffer of considerable survival value to stressed cells. 相似文献
67.
A review of childhood injuries at the Wesley Guild Hospital, a component of Obafemi Awolowo University Teaching Hospital Complex, Ile-Ife, Nigeria, showed that 1,471 patients seen in the children's emergency room during a period of 4 years (1992-1995) were there as a result of trauma, representing 9% of all patients seen. The case notes and accident and emergency cards of 1,224 were available for review. Ages ranged from 2 months to 15 years, with a mean of 6.9 years, and 40% of the patients were between 5 and 10 years of age. More males were affected than females, with a ratio of 1.5:1. Road traffic crashes were the most common causal factor, responsible for 324 injuries (26.5%). About 90% of these were pedestrians knocked down by automobiles and motorcycles. Passengers accounted for about 10% of the cases. Falls occurred in 305 patients (25%); 229 patients fell while on level ground either playing or running, accounting for 75%. There were 122 patients (10%) with misplaced foreign bodies; about 60% of these were recovered from the ears, and 26.3% from the nostrils. Edible seeds were the most common foreign bodies, followed by beads. Injuries from bites occurred in 108 patients, with dog and snake bites taking the lead. Burns, mainly from scalding, occurred in 89 patients. Other rare injuries were knife wounds, gunshot wounds, and injuries resulting from assaults. The home was the most common site of injury (570 patients, 46.7%) followed by streets or roadways (363 patients, 29.7%); 19.5% of injuries occurred at school. The most common anatomic region affected was the head and neck, followed by the limbs. One hundred ninety-seven patients (16%) had bony fractures, femurs being the most affected bone. Head injury was seen in 104 patients, representing 8.5%, although only 17 of these injuries were severe. There were 10 cases of abdominal injury and 9 cases of chest injury, representing 0.8 and 0.7%, respectively. Wound infection occurred in 6.4% of the patients. Death occurred in 19 patients, accounting for 1.6%; 10 of these patients had severe head injuries. Road traffic injuries and burns accounted for the greatest number of complications. The findings of this study suggest that trauma is an important factor in childhood morbidity and mortality in our environment, with road traffic injuries taking the lead. Preschool pedestrian children were most commonly affected, the majority of them on errands for their parents. We believe that the majority of these injuries are preventable. 相似文献
68.
Modulators of P-glycoprotein (P-gp) are often themselves transported out of cells, thereby limiting their effectiveness. It may be possible to develop more effective modulators of multidrug resistance by designing drugs that irreversibly block the function of P-gp. Therefore, we studied the effect of the mustard derivatives of fluphenazine (FPN) and trans-flupenthixol (FPT) on P-gp function. Both fluphenazine-mustard (FPN-M) and trans-flupenthixol-mustard (FPT-M) possessed alkylating activity, as assayed using 4-(p-nitrobenzyl) pyridine. Multidrug-resistant MCF-7/AdrR cells were incubated with FPN or FPN-M, or FPT or FPT-M for 1 h, washed for varying number of times in phosphate-buffered saline (PBS), then resuspended in medium containing [3H]vinblastine (VBL), and assayed for steady-state accumulation of the drug. Washing had far less of an effect on the ability of FPN-M and FPT-M to increase VBL accumulation compared to their parent compounds. After eight washes in excess PBS, the cells initially exposed to FPN or FPT accumulated only 30% and 50% of the initially accumulated drug, whereas the FPN-M- or FPT-M-treated cells accumulated approximately 75% and 90% of the control, respectively. FPN-M and FPT-M also increased the uptake and decreased the efflux of VBL from MDR cells despite repeated washing. We also examined the effects of these modulators on sensitivity of MDR cells to cytotoxic agents. FPN-M and FPT-M sensitized MCF-7/AdrR cells to VBL and doxorubicin to a greater extent than their parent compounds. These studies point out the potential of "irreversible" P-gp modulators to produce prolonged chemosensitization. 相似文献
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70.
An effective topical and regional anesthetic technique using 25% cocaine paste combined with intravenous midazolam hydrochloride was used in 554 patients undergoing functional endoscopic sinus surgery. The operative fields were excellent and all procedures were completed with little patient disturbance. Patients recovered rapidly from sedation and were usually fit for discharge on the same day. There were no anesthetic complications. The major surgical complication rate was 0.5%. 相似文献