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国内至今尚未有硝苯吡啶缓释制剂的报道。本文研制了硝苯吡啶控释微丸,并从体外溶出、家犬及人体试验诸方面进行评价。硝苯吡啶控释微丸体外释药基本符合一级方程(K=0.23h-1),而更符合Higuchi方程(K=37.05h1/2);家犬体内血药浓度较国外报道的缓释微丸更平稳,人体血药浓度也较平稳,10 min左右能达20ng/ml以上,维持在20~70ng/ml的时间约为15h,生物利用度较速释微丸略高。本文还对硝苯吡啶的药动学特性作了初步探讨,硝苯吡啶体内过程符合双室模型(t1/2β为3.5h)。 相似文献
506.
Metabolism of carcinogenic heterocyclic and aromatic amines by recombinant human cytochrome P450 enzymes 总被引:10,自引:4,他引:6
Hammons GJ; Milton D; Stepps K; Guengerich FP; Tukey RH; Kadlubar FF 《Carcinogenesis》1997,18(4):851-854
The N-hydroxylation of carcinogenic arylamines represents an initial step
in their metabolic activation. Animal studies have shown that this reaction
is catalyzed by the cytochrome P450 (P450) enzymes P450 1A1 and P450 1A2.
In this study, utilizing enzymes expressed in Escherichia coli (and
purified) or in human B-lymphoblastoid cells, the catalytic activities of
recombinant human P450 1A1, P450 1A2, and P450 3A4 for N- hydroxylation of
several carcinogenic arylamines were determined. P450 1A2 from both
expression systems catalyzed the N-hydroxylation of 4- aminobiphenyl and
the heterocyclic amines, 2-amino-3-methylimidazo[4,5- f/quinoline (IQ),
2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), and
2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). Rates were similar,
with values of 1.1-7.8 nmol/min/nmol P450. In contrast, P450 1A1 catalyzed
N-hydroxylation of only PhIP, and no activity was observed with P450 3A4.
Further kinetic analysis with purified P450 1A2 showed similar Km and Vmax
values for N-hydroxylation of the arylamines. Furafylline and fluvoxamine,
inhibitors of P450 1A2 activity in human liver microsomes, were found to be
inhibitory of the recombinant P450 1A2 N-hydroxylation activity. Results
from this study are supportive of a major role for human P450 1A2 in the
metabolic activation of arylamines.
相似文献
507.
M Hsin MB ChB J Speight MB ChB GJ Cooper MD FRCS 《International journal of clinical practice》1997,51(7):427-429
To establish the precision of anticoagulant control in the first three months after mechanical heart valve replacement, 53 patients from a consecutive series of 91 were telephoned and asked to read out their anticoagulation record. The levels of international normalised ratio (INR) were analysed by Rosendaal's method. Twenty-nine per cent of patient days were spent with an INR in the recommended range of 3.0-4.5. Warfarin dosage was increased at a median INR of 2.1 (interquartile range 1.7-2.3), unchanged at 2.7 (interquartile range 2.3-3.1) and decreased at 4.3 (interquartile range 3.6-5.1). Anticoagulant control is poor in the first three months after mechanical heart valve replacement. Data on the INR at which warfarin dosage is changed suggest either that recommended guidelines are not being followed or a reluctance to increase the dosage in patients receiving inadequate anticoagulation. 相似文献
508.
Analysis of signaling events associated with activation of neutrophil superoxide anion production by eosinophil granule major basic protein 总被引:2,自引:0,他引:2
This study was undertaken to identify the signaling events involved in activation of neutrophil superoxide anion (O2-) production by eosinophil granule major basic protein (MBP). MBP did not produce an immediate increase in the cytosolic free calcium concentration ([Ca2+]i), characteristic of phospholipase C activation, but did cause a gradual increase in [Ca2+]i in cytochalasin B-treated cells. Preincubation with 0.01 to 3 micrograms/mL pertussis toxin did not inhibit MBP-stimulated O2- production, and MBP did not stimulate an increase in diradylglycerol levels. MBP did stimulate a low level of phospholipase D activity, as measured by a time-dependent increase in phosphatidic acid and, in the presence of 0.5% ethanol, phosphatidylethanol. Inhibition of MBP-stimulated O2- production by genistein and Western blot analysis using an antiphosphotyrosine antibody showed tyrosine kinase activation by MBP. Calmodulin antagonists (calmidazolium and W-7) caused up to 80% inhibition of MBP- stimulated O2- production. In agreement with the pharmacologic sensitivity, MBP did not stimulate any 51Cr release. These data indicate that tyrosine kinase and calmodulin-dependent steps are involved in the noncytotoxic stimulation of neutrophil O2- production by MBP. 相似文献
509.
Mali WP; Puijlaert CB; Kouwenberg HJ; Klinge J; Donckerwolcke RA; Geijskes BG; Overbosch EH; Rosenbusch GJ; Ludwig WW; Feldberg MA 《Radiology》1987,165(2):391-394
Percutaneous transluminal renal angioplasty (PTRA) was performed in 12 children and adolescents with renal artery stenosis. Patients were divided into three groups: those with a short stenosis in the middle or distal part of the renal artery (n = 5), those with a short stenosis at or near the origin of the renal artery (n = 3), and those with a long stenosis at or near the origin (n = 4). The patients in the first group responded to PTRA. Those in the second group had a poor clinical response, and dilation was unsuccessful in the patients in the third group, who remained hypertensive. The location and length of the renal artery stenosis and its underlying cause appear to be important in determining the results of PTRA. 相似文献
510.
The arthrographic image quality and relative morbidity resulting from use of Omnipaque 300 (iohexol), Hexabrix 320 (ioxaglate sodium meglumine), and Isopaque Coronar 370 (metrizoate) were compared in a prospective double-blind study performed with 120 patients. Radiographs obtained 2, 5, 10, 15, 20, and 25 minutes after injection were judged for diagnostic quality. Relative morbidity was evaluated by the physician during the examination and later by the patient via a questionnaire. Hexabrix demonstrated the best and most persistent diagnostic quality over serial radiographs (P less than .05). Omnipaque caused significantly less postprocedural pain (P less than .05). The other types of discomfort measured did not indicate statistically significant differences in morbidity resulting from the three contrast agents. 相似文献