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Hemmings SM Kinnear CJ Lochner C Niehaus DJ Knowles JA Moolman-Smook JC Corfield VA Stein DJ 《Psychiatry research》2004,128(2):175-182
There is increasing evidence that obsessive-compulsive disorder (OCD) is mediated by genetic factors. Although the precise mechanism of inheritance is unclear, recent evidence has pointed towards the involvement of the serotonergic and dopaminergic systems in the disorder's development. Furthermore, early-onset OCD appears to be a subtype that exhibits distinct clinical features and that is associated with greater familial loading. In the present investigation, South African OCD patients (n=252) were stratified according to age of onset and were clinically assessed. Additionally, selected variants in genes encoding serotonergic and dopaminergic components were investigated in a Caucasian OCD subset (n=180). This subgroup was further stratified to evaluate the role that these candidate genes may play in the genetically homogeneous Afrikaner subset (n=80). Analysis of the clinical data revealed an association between early age of onset and an increased frequency of tics, Tourette's disorder, and trichotillomania (TTM). The genetic studies yielded statistically significant results when the allelic distributions of genetic variants in the dopamine receptor type 4 gene (DRD4) were analysed in the Caucasian OCD cohort. These data support a role for the dopaminergic system, which may be relevant to the development of early-onset OCD. 相似文献
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Dunroy HM Adams L Corfield DR Morrell MJ 《Respiratory physiology & neurobiology》2003,136(2-3):179-186
Some patients with lung disease retain CO(2), while others with similar lung function do not. This could be explained if CO(2) retainers had a pre-existing low hypercapnic ventilatory response (HCVR) and, from this, a tendency to retain CO(2). To test if such a phenomenon exists in healthy people, we determined the change in end-tidal P(CO(2)) (deltaPET(CO(2))) produced by the addition of a dead-space (DS), during wakefulness and sleep, and related this to the HCVR measured awake. The group mean (n=14) HCVR slope was 2.2+/-1.1 (S.D.) L min(-1) mmHg(-1). The deltaPET(CO(2)) with the application of DS was 1.6+/-1.6 mmHg awake and 2.6+/-2.2 mmHg asleep. During wakefulness the deltaPET(CO(2)) with DS did not correlate with the HCVR slope. However, during sleep, four subjects had a marked increase in the deltaPET(CO(2)) (3.7, 4.3, 6.2, 8.0 mmHg) and a relatively low HCVR (slope 1.5, 1.7, 1.5, 1.7 L min(-1) mmHg(-1), respectively). We speculate that such individuals, should they develop lung disease, may be predisposed to retain CO(2). 相似文献
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The ventilatory responses to hypercapnia and hypoxia are reduced during sleep compared to wakefulness. However, sleep-related increases in upper airways' resistance could reduce these ventilatory responses independently of any change in the neural output to the respiratory pump muscles. It is therefore possible that respiratory chemosensitivity, per se, is unchanged by sleep. To investigate this, four healthy male subjects were mechanically ventilated to abolish spontaneous respiratory muscle activity. The response to transient isocapnic hypoxia was quantified from the magnitude of the electromyographic activity induced in the diaphragm and from the associated reduction in peak inspiratory pressure; these indicies of respiratory motor output will not be affected by any sleep-related changes in upper airways' resistance. In all individuals, the responses to hypoxia were markedly attenuated during sleep compared to wakefulness. These observations, assessing the 'neuromuscular' ventilatory response, are consistent with a sleep-related reduction in respiratory chemosensitivity that is independent of any changes that may be due to increases in upper airways' resistance. 相似文献
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The relative bioavailability of metoprolol following oral and rectal administration to volunteers and patients 总被引:1,自引:0,他引:1
F.M. de Stoppelaar L.M.L. Stolk A.J. Beysens J.L.M. Stappers AP.M. Gorgels 《Pharmacy World & Science》1999,21(5):233-238
The pharmacokinetics, efficacy and safety of metoprolol tartrate 25 mg fatty suppositories were studied in 5 healthy volunteers and in 8 patients suffering from instable angina pectoris. Metoprolol 25 mg capsules were used as a control oral dosage form. Metoprolol showed a considerable rectal bioavailability (AUC, C max) and was absorbed quickly from the rectum (T max). In both groups rectal bioavailability was comparable. However, oral bioavailability was much lower in the volunteer group than in the patient group. Furthermore, ratios of metoprolol/aOHmetoprolol concentrations in plasma and urine gave an indication for a partial avoidance of the first pass effect after rectal administration. Further research is necessary to define an exact rectal dosage of metoprolol. In all patients, a substantial drop in heart rate, systolic and diastolic blood pressure was seen after administration of the first suppository. Metoprolol suppositories appear to be an effective, safe and suitable alternative for patients who are in need for beta blocking medication and who are unable to take oral medication for a certain amount of time. 相似文献
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Scintiscans of liver and spleen using technetium 99m sulphur colloid in 15 infants with extrahepatic biliary atresia and 11 infants with severe obstructive jaundice (7 with genetic deficiency of alpha 1-antitrypsin) showed similar hepatic size, pattern of isotope uptake, and splenic abnormality with no distinguishing features. In 37 older children with a variety of liver disorders, the scan was invaluable in showing filling defects in five instances. Selenomethionine was taken up not only by the two filling defects due to hepatoblastoma but also in a haemangioendothelioma. In the remaining patiens liver scanning confirmed hepatic abnormality and the necessity for more specific invasive diagnostic investigations. 相似文献
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