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21.
P. H. Whiting A. W. Thomson J. G. Simpson 《International journal of experimental pathology》1983,64(6):693-701
Sprague-Dawley rats received cyclosporin A (25 mg/kg) together with either the aminoglycoside gentamicin (50 mg/kg) or one of 3 cephalosporin antibiotics (100 mg/kg) daily for 14 days. Only minor impairment of renal or hepatic function was observed when either cyclosporin A or gentamicin was given on its own and no abnormality was seen in response to cephalosporins. However, concomitant administration of cyclosporin A and gentamicin caused acute renal failure, accompanied by cyclosporin A-induced damage to the proximal straight tubule and gentamicin-induced proximal convoluted tubular cell necrosis. In contrast, the structural abnormalities present in the 3 groups given cephalosporins in addition to cyclosporin A were attributable only to the immune suppressant. Liver functional changes previously found only at higher doses of cyclosporin A were observed in the cyclosporin A/gentamicin group and there was some evidence of possible interactions between cyclosporin A and each cephalosporin affecting liver function. The results indicate that treatment of infection with cephalosporin antibiotics or a less nephrotoxic aminoglycoside is preferable to gentamicin in cyclosporin A-treated patients. 相似文献
22.
Bruce R. Whiting Timothy A. Holden Barry S. Brunsden Charles C. Finley Margaret W. Skinner 《Journal of digital imaging》2008,21(3):323-328
While 3-dimensional (3D) imaging by computed tomography has long been desirable for research and treatment of cochlear-implant
patients, technical challenges have limited its wide application. Recent developments in scanner hardware and image processing
techniques now allow image quality improvements that make clinical applications feasible. Validation experiments were performed
to characterize a new methodology and its imaging performance. 相似文献
23.
Whiting H 《Health and social service journal》1984,94(4881):109, 111
24.
William C Stanley Bin Li Douglas W Bonhaus Lowell G Johnson Keiho Lee Seth Porter Keith Walker Greg Martinez Richard M Eglen Roger L Whiting Sharath S Hegde 《British journal of pharmacology》1997,121(8):1803-1809
- Inhibitory modulation of sympathetic nerve function may have a favourable impact on the progression of congestive heart failure. Nepicastat is a novel inhibitor of dopamine-β-hydroxylase, the enzyme which catalyses the conversion of dopamine to noradrenaline in sympathetic nerves. The in vitro pharmacology and in vivo catecholamine modulatory effects of nepicastat were investigated in the present study.
- Nepicastat produced concentration-dependent inhibition of bovine (IC50=8.5±0.8 nM) and human (IC50=9.0±0.8 nM)dopamine-β-hydroxylase. The corresponding R-enantiomer (RS-25560-198) was approximately 2–3 fold less potent than nepicastat. Nepicastat had negligible affinity (>10 μM) for twelve other enzymes and thirteen neurotransmitter receptors.
- Administration of nepicastat to spontaneously hypertensive rats (SHRs) (three consecutive doses of either 3, 10, 30 or 100 mg kg−1, p.o.; 12 h apart) or beagle dogs (0.05, 0.5, 1.5 or 5 mg kg−1, p.o.; b.i.d., for 5 days) produced dose-dependent decreases in noradrenaline content, increases in dopamine content and increases in dopamine/noradrenaline ratio in the artery (mesenteric or renal), left ventricle and cerebral cortex. At the highest dose studied, the decreases in tissue noradrenaline were 47%, 35% and 42% (in SHRs) and 88%, 91% and 96% (in dogs) in the artery, left ventricle and cerebral cortex, respectively. When tested at 30 mg kg−1, p.o., in SHRs, nepicastat produced significantly greater changes in noradrenaline and dopamine content, as compared to the R-enantiomer (RS-25560-198), in the mesenteric artery and left ventricle.
- Administration of nepicastat (2 mg kg−1, b.i.d, p.o.) to beagle dogs for 15 days produced significant decreases in plasma concentrations of noradrenaline and increases in plasma concentrations of dopamine and dopamine/noradrenaline ratio. The peak reduction (52%) in plasma concentration of noradrenaline and the peak increase (646%) in plasma concentration of dopamine were observed on day-6 and day-7 of dosing, respectively.
- The findings of this study suggest that nepicastat is a potent, selective and orally active inhibitor of dopamine-β-hydroxylase which produces gradual modulation of the sympathetic nervous system by inhibiting the biosynthesis of noradrenaline. This drug may, therefore, be of value in the treatment of cardiovascular disorders associated with over-activation of the sympathetic nervous system, such as congestive heart failure.
25.
D. P. Middaugh D. D. Whiting 《Archives of environmental contamination and toxicology》1995,29(4):535-539
Embryonic inland silversides, Menidia beryllina, in the early blastula stage were exposed to the water-soluble fraction (WSF) of No. 2 Fuel oil and the oil dispersants Corexit 7664® and 9527®, singly and in combination. An ordinal ranking system was used to score observed daily craniofacial, cardiovascular, and skeletal responses in control embryos and those exposed to 1%, 10%, and 100% concentrations of the WSF of No. 2 Fuel oil, the dispersants Corexit 7664® and 9527® applied at the recommended field application concentrations, and the combination of No. 2 Fuel oil and respective dispersants in seawater. The non-parametric Kruskal-Wallis analysis of variance (ANOVA) and post hoc analyses were used to identify statistically significant differences for control embryos and those exposed to No. 2 Fuel oil and dispersants.Embryos exposed to No. 2 Fuel oil in 20 salinity seawater showed significant (0.01) responses only at the 100% WSF concentration. Corexit 7664® tested singly elicited significant responses at 10% and 100% concentrations. When No. 2 Fuel oil and Corexit 7664® were combined at recommended field application concentrations of the dispersant, the oil and dispersant mixture resulted in significant (0.01) responses at 1%, 10%, and 100% exposure concentrations. In contrast, Corexit 9527® did not cause significant responses at the three test concentrations of 1%, 10%, and 100% of the recommended field application rate. However, when No. 2 Fuel oil and Corexit 9527® were combined in seawater, the 10% and 100% exposure concentrations resulted in statistically significant (0.01) embryonic responses, relative to controls. Chemical analyses indicated that both dispersants increased the total WSF of No. 2 Fuel oil in seawater.Contribution No. 897 of the Gulf Breeze Environmental Research Laboratory 相似文献
26.
27.
The ventromedial nucleus of the hypothalamus (VMH) is a key nucleus for regulating homeostatic, neuroendocrine, and behavioral functions. We conducted immunocytochemical analyses by using antisera directed against gamma-aminobutyric acid (GABA), its synthetic enzyme glutamic acid decarboxylase (GAD67), GABA-A receptor subunits (alpha2, beta3, epsilon), estrogen receptor-alpha, and Neuropeptide Y (NPY) in the region of the VMH in embryonic mice to identify potential patterning elements for VMH formation. Cells and fibers containing GABA and GAD67 encircled the primordial VMH as early as embryonic day 13 (E13) when the cytoarchitecture of the VMH was not recognizable by Nissl stain. At E16-17 the cytoarchitecture of the VMH became recognizable by Nissl stain as GABAergic fibers invaded the nucleus, continued postnatally, and by adulthood the density of GABAergic fibers was greater inside than outside the VMH. GABA-A receptor subunit expression (beta3 by E13 and alpha2 by E15) within the primordial VMH suggested potential sensitivity to the surrounding GABA signal. Brain slices were used to test whether fibers from distal or proximal sites influenced VMH development. Coronal Vibratome slices were prepared and maintained in vitro for 0-3 days. Nissl stain analyses showed a uniform distribution of cells in the region of the VMH on the day of plating (E15). After 3 days in vitro, cellular aggregation suggesting VMH formation was seen. Nuclear formation in vitro suggests that key factors resided locally within the coronal plane of the slices. It is suggested that either GABA intrinsic to the region nearby the VMH directly influences the development and organization of the VMH, or along with other markers provides an early indicator of pattern determination that precedes the cellular organization of the VMH. 相似文献
28.
A. K. Wagner K. Wyss B. Gandek P. M. Kilima S. Lorenz D. Whiting 《Quality of life research》1999,8(1-2):101-110
The objective of the study was to translate and adapt the SF-36 Health Survey for use in Tanzania and to test the psychometric properties of the Kiswahili SF-36. A cross-sectional study was conducted as part of a household survey of a representative sample of the adult population of Dar es Salaam, Tanzania. The IQOLA method of forward and backward translation was used to translate the SF-36 into Kiswahili. The translated questionnaire was administered by trained interviewers to 3,802 adults (50% women, mean (SD) age 31 (13) years, 50% married and 60% with primary education). Data quality and psychometric assumptions underlying the scoring of the eight SF-36 scales were evaluated for the entire sample and separately for the least educated subgroup (n=402), using multitrait scaling analysis. Forward and backward translation procedures resulted in a Kiswahili SF-36 that was considered conceptually equivalent to the US English SF-36. Data quality was excellent: only 1.2% of respondents were excluded because they answered less than half of the items for one or more scales; ninety percent of respondents answered mutually exclusive items consistently. Median item–scale correlations across the eight scales ranged from 0.47 to 0.81 for the entire sample. Median scaling success rates were 100% (range 87.5–100.0). The median internal consistency reliability of the eight scales for the entire sample was 0.81 (range 0.70–0.92). Floor effects were low and ceiling effects were high on five of the eight scales. Results for n=402 people without formal education did not differ substantially from those of the entire sample. The results of data quality and psychometric tests support the scoring of the eight scales using standard scoring algorithms. The Kiswahili translation of the SF-36 may be useful in estimating the health of people in Dar es Salaam. Evidence for the validity of the SF-36 for use in Tanzania needs to be accumulated. 相似文献
29.
C Sur S J Farrar J Kerby P J Whiting J R Atack R M McKernan 《Molecular pharmacology》1999,56(1):110-115
Pharmacological study of rat thalamic gamma-aminobutyric acidA (GABAA) receptors revealed the presence of two distinct populations, namely, diazepam-sensitive and diazepam-insensitive [3H]Ro15-4513 binding sites accounting for 94 +/- 2% (1339 +/- 253 fmol/mg protein) and 6 +/- 2% (90 +/- 44 fmol/mg protein) of total sites, respectively. Thalamic diazepam-insensitive sites exhibited a pharmacology that was distinct from diazepam-sensitive sites but comparable to that of the alpha4beta3gamma2 subtype of the GABAA receptor stably expressed in L(tk-) cells. Immunoprecipitation experiments with a specific anti-alpha4-antiserum immunoprecipitated 20 and 7% of total thalamic [3H]muscimol and [3H]Ro15-4513 sites, respectively. Combinatorial immunoprecipitation using antisera against the alpha4, gamma2, and delta subunit revealed that alpha4delta- and alpha4gamma2-containing receptors account for 13 +/- 2 and 8 +/- 3% of [3H]muscimol sites from thalamus, respectively. It also indicated that all delta subunits coexist with an alpha4 subunit in this brain region. In conclusion, our results show that in rat thalamus both alpha4betagamma2 and alpha4betadelta subtypes are expressed but alpha4betadelta is the major alpha4-containing GABAA receptor population. 相似文献
30.