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111.
112.

Background

We have recently shown that human epididymis protein 4 (HE4) levels correlate with the severity of cystic fibrosis (CF) lung disease. However, there are no data on how HE4 levels alter in patients receiving CFTR modulating therapy.

Methods

In this retrospective clinical study, 3 independent CF patient cohorts (US-American: 29, Australian: 12 and Irish: 19 cases) were enrolled carrying at least one Class III CFTR CF-causing mutation (p.Gly551Asp) and being treated with CFTR potentiator ivacaftor. Plasma HE4 was measured by immunoassay before treatment (baseline) and 1–6?months after commencement of ivacaftor, and were correlated with FEV1 (% predicted), sweat chloride, C-reactive protein (CRP) and body mass index (BMI).

Results

After 1?month of therapy, HE4 levels were significantly lower than at baseline and remained decreased up to 6?months. A significant inverse correlation between absolute and delta values of HE4 and FEV1 (r?=??0.5376; P?<?.001 and r?=??0.3285; P?<?.001), was retrospectively observed in pooled groups, including an independent association of HE4 with FEV1 by multiple regression analysis (β?=??0.57, P?=?.019). Substantial area under the receiver operating characteristic curve (ROC-AUC) value was determined for HE4 when 7% mean change of FEV1 (0.722 [95% CI 0.581–0.863]; P?=?.029) were used as classifier, especially in the first 2?months of treatment (0.806 [95% CI 0.665–0.947]; P?<?.001).

Conclusions

This study shows that plasma HE4 levels inversely correlate with lung function improvement in CF patients receiving ivacaftor. Overall, this potential biomarker may be of value for routine clinical and laboratory follow-up of CFTR modulating therapy.  相似文献   
113.
Lasers in Medical Science - Using light sources in phototherapy has presented promising results regarding several types of facial and body skin affections for centuries. The neodymium-doped yttrium...  相似文献   
114.
We investigated the effects of the noble gas argon on the expression of locomotor sensitization to amphetamine and amphetamine-induced changes in dopamine release and mu-opioid neurotransmission in the nucleus accumbens. We found (1) argon blocked the increase in carrier-mediated dopamine release induced by amphetamine in brain slices, but, in contrast, potentiated the decrease in KCl-evoked dopamine release induced by amphetamine, thereby suggesting that argon inhibited the vesicular monoamine transporter-2; (2) argon blocked the expression of locomotor and mu-opioid neurotransmission sensitization induced by repeated amphetamine administration in a short-term model of sensitization in rats; (3) argon decreased the maximal number of binding sites and increased the dissociation constant of mu-receptors in membrane preparations, thereby indicating that argon is a mu-receptor antagonist; (4) argon blocked the expression of locomotor sensitization and context-dependent locomotor activity induced by repeated administration of amphetamine in a long-term model of sensitization. Taken together, these data indicate that argon could be of potential interest for treating drug addiction and dependence.  相似文献   
115.
The actinobacterium strain ABH26 closely related to Saccharothrix xinjiangensis, isolated from an Algerian Saharan soil sample, exhibited highly antagonist activity against Gram-positive bacteria, yeasts and filamentous fungi. Its ability to produce antimicrobial compounds was investigated using several solid culture media. The highest antimicrobial activity was obtained on Bennett medium. The antibiotics secreted by strain ABH26 on Bennett medium were extracted by methanol and purified by reverse-phase HPLC using a C18 column. The chemical structures of the compounds were determined after spectroscopic (1H NMR, 13C NMR, 1H-1H COSY and 1H-13C HMBC spectra), and spectrometric (mass spectrum) analyses. Two new cyanogriside antibiotics named cyanogriside I (1) and cyanogriside J (2), were characterized along with three known caerulomycins, caerulomycin A (3), caerulomycin F (4) and caerulomycinonitrile (5). This is the first report of cyanogrisides and caerulomycins production by a member of the Saccharothrix genus. The minimum inhibitory concentrations (MIC) of these antibiotics were determined against pathogenic microorganisms.  相似文献   
116.
117.
Summary We present a case of blindness and Anton’s syndrome in a psychiatric patient with late diagnosis of a giant frontal meningioma. The criteria for advanced diagnostic imaging in the psychiatric population are discussed. We conclude that MR or CT scan is indicated in psychiatric in-patients who fail to improve with standard psychiatric treatment. This strategy should be submitted to a cost-benefit analysis.  相似文献   
118.
A drug interaction refers to an event in which the usual pharmacological effect of a drug is modified by other factors, most frequently additional drugs. When two drugs are administered simultaneously, or within a short time of each other, an interaction can occur that may increase or decrease the intended magnitude or duration of the effect of one or both drugs. Drugs may interact on a pharmaceutical, pharmacokinetic or pharmacodynamic basis. Pharmacodynamic interactions arise when the alteration of the effects occurs at the site of action. This is a wide field where not only interactions between different drugs are considered but also drug and metabolites (midazolam/alpha-hydroxy-midazolam), enantiomers (ketamine), as well as phenomena such as tolerance (nordiazepam) and sensitization (diazepam). Pharmacodynamic interactions can result in antagonism or synergism and can originate at a receptor level (antagonism, partial agonism, down-regulation, up-regulation), at an intraneuronal level (transduction, uptake), or at an interneuronal level (physiological pathways). Alternatively, psychotropic drug interactions assessed through quantitative pharmaco-EEG can be viewed according to the broad underlying objective of the study: safety-oriented (ketoprofen/theophylline, lorazepam/diphenhydramine, granisetron/haloperidol), strictly pharmacologically-oriented (benzodiazepine receptors), or broadly neuro-physiologically-oriented (diazepam/buspirone). Methodological issues are stressed, particularly drug plasma concentrations, dose-response relationships and time-course of effects (fluoxetine/buspirone), and unsolved questions are addressed (yohimbine/caffeine, hydroxizyne/alcohol).  相似文献   
119.
OBJECTIVES: The aim of this study is to evaluate the effect of ZnSO(4) addition to a conventional glass ionomer and a resin-modified glass ionomer on solubility, flexural strength, zinc and fluoride (F) release, and Streptococcus mutans growth inhibition. METHODS: 5 or 10% ZnSO(4) was added to Vitremer and Ketac-Fil powders. Solubility test was performed based on ISO 7489. Flexural strength was determined by 3-point bending test based on ISO 4049. Zn release/uptake was determined by atomic emission spectrometry; F release/uptake was measured using a F-specific electrode. Both release measurements were performed for 15 d before and 15 d after recharging. Antibacterial test was conducted according to agar plate methods against S. mutans, by measuring the inhibition halos in 1-h and 15-d specimens. Data were analyzed by ANOVA. RESULTS: Solubility increased with higher ZnSO(4) content, but remained below the ISO 7489 limit. Flexural strength was not affected by ZnSO(4) addition, and Vitremer performed better than Ketac-Fil. The control materials released no zinc. Vitremer with 10% ZnSO(4) released the highest amount of zinc. Fluoride release was similar for Ketac-Fil and Vitremer. In both cases, the highest amounts were released in the first 24 h. The growth inhibition halo of S. mutans was similar for both materials with highest content of ZnSO(4) and occurred only with 1-h specimens. SIGNIFICANCE: Zinc addition decreased microorganisms growth and improved fluoride release, without significantly affecting the materials' flexural strength and solubility.  相似文献   
120.
The increased number of lymphocytes in airways during an asthmatic response is believed to be the result of increased recruitment of these cells. However, it is possible that a decreased apoptotic rate could also contribute to the increased number. The aim of the present study was to investigate whether allergen airway provocation influences the apoptotic phenotype of lung and peripheral blood lymphocytes (PBL) in subjects with atopic asthma. Bronchoalveolar lavage (BAL) lymphocytes and PBL from 12 asthmatic subjects previously challenged with allergen (n = 7) or saline (n = 5) were exposed to the apoptotic stimulus tributyltin (TBT) in vitro and assayed for apoptosis. Airway allergen provocation resulted in decreased sensitivity of BAL lymphocytes to TBT-induced apoptosis, with 42.2% (range 33.9-62.5%) apoptotic cells before challenge versus 23.5% (range 15.3-42.4%) after challenge, while PBL were unaffected. The increased apoptosis resistance correlated with higher numbers of Bcl-2-expressing lymphocytes. Interestingly, baseline caspase-3-like activity was significantly elevated in viable BAL lymphocytes compared with viable PBL, and was unaltered by allergen exposure. In conclusion, allergen inhalation renders bronchoalveolar lavage lymphocytes more resistant to apoptosis while peripheral blood lymphocytes were not influenced at all, indicating that the apoptotic phenotype of airway lymphocytes may play a role in asthmatic inflammation.  相似文献   
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