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101.
Preliminary pharmacologic evidence suggests that tiagabine, a new presynaptic gamma-aminobutyric acid-uptake inhibitor developed as an antiepileptic drug, may also relieve spasticity. This pilot study assessed the drug's efficacy in 14 children with congenital or acquired spastic quadriplegia and concomitant intractable epilepsy refractory to treatment with multiple antiepileptic drugs. The primary outcome variable was change in motor function; the secondary outcome was change in seizure frequency. Tiagabine was initiated at 0.1-0.2 mg/kg/day and then gradually titrated upward until seizures ceased, adverse effects supervened, or the maximum dose of 1.1 mg/kg/day was reached. When a modified Ashworth scale was used to assess motor function, a mean improvement of approximately 50% was observed. Common findings included improved tone, strength, coordination, range of motion, and relaxation of extremities, with less ataxia and wobbling. Mean reduction in seizure frequency was 50-74%. Randomized, double-blind controlled studies are needed to confirm the suggested efficacy of tiagabine in relieving chronic spasticity in children with neurodevelopmental disorders.  相似文献   
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PURPOSE: To report the association between colonization of contact lenses with Streptococcus pneumoniae and the observation of corneal infiltrative events in a group of patients wearing disposable hydrogel lenses on an extended-wear schedule. METHODS: In a prospective clinical trial, 330 patients wore disposable hydrogels on a 6-night extended-wear and replacement schedule. The contact lens, lid, and conjunctival microbiota of these subjects was analyzed at frequent intervals and at the time of an adverse event. RESULTS: Streptococcus pneumoniae was an uncommon isolate and was recovered from only one of the 3,763 conjunctival samples, five (0.1%) of the 3,764 lid samples, and 33 (0.8%) of the 4,315 contact lens samples. Of the 33 lens samples, 10 (30%) were associated with corneal infiltrative events. Many of the events were mild inflammatory responses and resolved rapidly on discontinuation of lens wear. The presence of S. pneumoniae on the contact lens was associated with a significant risk of development of corneal infiltrates (odds ratio, 3.0; p = 0.0227, logistic-regression analysis). CONCLUSIONS: Presence of S. pneumoniae on hydrogel lenses is a significant risk factor for the development of corneal infiltrates.  相似文献   
104.
Anorexia nervosa (AN) is associated with a reduced metabolically active fat-free mass (FFM) and basal metabolic rate (BMR). Excessive refeeding results in major fat deposition which is not well tolerated by patients. Prediction of BMR is, therefore, a clinical issue during refeeding, but measurement by indirect calorimetry is time-consuming and not widely available. The study aim was to determine if and when BMR could be estimated from prediction formulas based on FFM derived from bioelectrical impedance analysis (BIA) in AN patients during refeeding. Indirect calorimetry and BIA were prospectively measured bi-weekly in 9 AN patients (body mass index 13.7 +/- 0.5 kg/m2) for 10 weeks of refeeding. Initial BMR was 969 +/- 46.7 kcal/d and 27.7 +/- 1.4 kcal/kg FFM, and at week 10 increased to 1360 +/- 44.6 kcal/d and 35.8 +/- 0.8 kcal/kg FFM. While correlations improved with increasing weight, FFM and body mass index, prediction formulas are insufficient to permit prediction of BMR based on weight or FFM, even after 10 weeks of refeeding. To allow for optimal nutritional support, indirect calorimetry measurements may be useful in the early weeks of refeeding because of a large variability of basal metabolic rate between patients.  相似文献   
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To eliminate the operation of organizational factors during crossmodal information processing, we compared mentally retarded adolescents, CA-matched nonretarded adolescents, and MA-matched children in a same-different decision task in which dyadic sequences were presented within and across the visual and auditory modalities. Decision times for correct "different" responses were greater for the CA-matched group than for the EMR and MA-matched groups, with all groups showing longest times for the visual-auditory dyads and shortest times for dyads in which both stimuli were visual. Differences between the auditory-auditory and auditory-visual dyads were negligible, and increments from visual-visual to visual-auditory dyads were significantly greater than from auditory-auditory to auditory-visual dyads in the EMR and MA groups. Results support a concept of greater visual dominance by the retarded and MA-matched groups rather than slower crossmodal attention switching, per se.  相似文献   
107.
The use of chemotherapy has led to improved treatment outcome for some pediatric patients with medulloblastoma. We have used a pre-radiation chemotherapy regimen consisting of vincristine and CDDP. The 9L gliosarcoma implanted intracranially and subcutaneously in the same animals was used as a preclinical model system to assess the efficacy of treatment combinations including: vincristine, CDDP, cyclo-phosphamide, etanidazole and radiation. The experimental endpoints were percent increase-in-lifespan, tumor growth delay and tumor cell survival. Both the tumor growth delay and percent increase-in-lifespan improved as the number of agents included in the chemotherapy regimen increased. so that the chemotherapy regimen including all four agents (ETA/VIN/CDDP/CTX) resulted in the greatest tumor growth delay (23.6 +/- 1.5 days) and the greatest increase-in-lifespan (35.8%). When radiation (20 Gray, single dose) was added to the treatment regimens the combinations of ETA/CTX/X-ray and ETA/VIN/CDDP/CTX/X-ray resulted in equivalent tumor growth delays (25.2 +/- 1.3 days and 25.8 +/- 1.7 days, respectively), while the greatest increase-in-lifespan (39.1%) was obtained with the five agent combination. The response of the 9L gliosarcoma to CDDP and cyclophosphamide over a dosage range was very similar to that of the murine FSaII fibrosarcoma. Our results indicate that etanidazole may be an effective chemosensitizer of combination chemotherapy and combined modality treatment regimens for brain tumors.  相似文献   
108.
Monette  FC; Holden  SA 《Blood》1982,60(2):527-530
Since exogenous hemin has been shown to exert a variety of stimulatory effects on erythroid cells, including the augmentation of hemoglobin synthesis, we determined its effect on early stages of erythroid development by employing clonal cells assays. The addition of hemin at a concentration of 2 X 10(-4) M to cultures of normal murine marrow substantially increased the observed number of primitive BFU-E, which was in contrast to its lack of an effect on more mature erythroid colony-forming cells. This cell-specific enhancement of primitive BFU-E resulted in marrow frequencies equivalent to or exceeding those reported in the presence of "burst-promoting activity." In the presence of hemin, the number of BFU-E was also observed to be linearly related to the number of cells plated at very low plating densities, and the cell titration curve was observed to extrapolate to the origin. The evidence suggests that hemin may be a primary growth regulator of early developmental stages of erythroid progenitor cells.  相似文献   
109.
110.
William L Holden 《Drug safety》2003,26(12):853-862
Given the current status of benefit-risk analysis as a largely qualitative method, two techniques for a quantitative synthesis of a drug's benefit and risk are proposed to allow a more objective approach. The recommended methods, relative-value adjusted number-needed-to-treat (RV-NNT) and its extension, minimum clinical efficacy (MCE) analysis, rely upon efficacy or effectiveness data, adverse event data and utility data from patients, describing their preferences for an outcome given potential risks. These methods, using hypothetical data for rheumatoid arthritis drugs, demonstrate that quantitative distinctions can be made between drugs which would better inform clinicians, drug regulators and patients about a drug's benefit-risk profile. If the number of patients needed to treat is less than the relative-value adjusted number-needed-to-harm in an RV-NNT analysis, patients are willing to undergo treatment with the experimental drug to derive a certain benefit knowing that they may be at risk for any of a series of potential adverse events. Similarly, the results of an MCE analysis allow for determining the worth of a new treatment relative to an older one, given not only the potential risks of adverse events and benefits that may be gained, but also by taking into account the risk of disease without any treatment. Quantitative methods of benefit-risk analysis have a place in the evaluative armamentarium of pharmacovigilance, especially those that incorporate patients' perspectives.  相似文献   
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