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Umberto Capitanio Pierre I Karakiewicz Claudio Jeldres Alberto Briganti rea Gallina Nazareno Suardi rea Cestari Giorgio Guazzoni rea Salonia Francesco Montorsi 《International journal of urology》2009,16(5):526-529
The objective of this study was to test the external validity of a previously developed nomogram for the prediction of Gleason score upgrading (GSU) between biopsy and radical prostatectomy (RP). The study population consisted of 973 assessable patients treated with RP at a tertiary care institution. The accuracy of the nomogram was quantified with the receiver operating characteristics curve-derived area under the curve. The performance characteristics (predicted vs observed rate of GSU) were tested within a calibration plot. Overall, GSU was recorded in 39.8% ( n = 387) of patients at RP. Of patients with GSU, 70 (18.1%), 23 (5.9%) and 32 (8.3%), respectively, had extracapsular extension, seminal vesicle invasion and lymph node invasion. The accuracy of the nomogram was 74.9% (confidence interval 72.1–77.6%). The model tended to underestimate the observed rate of GSU and the discordance between the predicted and observed rate of GSU ranged from −7 to +10%. The current tool represents the most accurate method of predicting GSU between biopsy and RP. Nonetheless it is not perfect and its performance characteristics should be known prior to its use in clinical decision-making. 相似文献
996.
Grumelli C Berghuis P Pozzi D Caleo M Antonucci F Bonanno G Carmignoto G Dobszay MB Harkany T Matteoli M Verderio C 《Molecular and cellular neurosciences》2008,39(3):314-323
Calpains are a family of calcium-dependent proteases with abundant expression in the CNS, and potent in cleaving some synaptic components. Assessment of calpain activity by its fluorescent substrate, Boc-Leu-Met-CMAC, revealed that cultured neurons display a significant level of constitutive enzyme activity. Notably, calpain activity differs in distinct neuronal populations, with a significantly higher level of activity in GABAergic cells. Using selectively-enriched cultures of fast-spiking GABAergic interneurons, we show that calpain activity partially contributes to the post-translational down regulation of SNAP-25, a calpain substrate, in differentiated GABA cells. In addition, we demonstrate that SNAP-25 is cleaved by calpain in response to acute seizures induced by intraperitoneal kainate injection in vivo. These data indicate that calpains in neurons are active even at physiological calcium concentrations and that different levels of calpain activation in selected neuron subtypes may contribute to the pattern of synaptic protein expression. 相似文献
997.
Giorgio L Colombo Mauro Caruggi Sergio Di Matteo Alessandro Rossi 《Neuropsychiatric Disease and Treatment》2008,4(5):967-976
Objective
To evaluate the cost-effectiveness of aripiprazole and olanzapine in patients with schizophrenia.Methods
Data from a double-blind, randomized study demonstrating the efficacy of aripiprazole and olanzapine were used to observe new incidence of metabolic syndrome (26-week therapy) and to model the risk of developing diabetes over 5 years of therapy. Cumulative incidence of metabolic syndrome was compared using Kaplan–Meier estimates; diabetes risk was estimated using a validated, general population risk-prediction model. Economic assessment was conducted from the third-party payer perspective by evaluating pharmacotherapy costs of treating schizophrenia and medical costs associated with treating adverse metabolic effects in a hypothetical cohort of 1000 patients. Resource utilization and costs were derived from the underlying study and published data, using a 3% rate to discount costs and benefits.Results
For the patients switched from olanzapine to aripiprazole, treatment with aripiprazole was a dominant cost-saving strategy. Use of aripiprazole avoided 184 events of metabolic syndrome over 26 weeks of treatment, contributing to a real-world (RW) cost savings of €2.53 per patient and a total savings of approximately €465.52 over a 5-year period. For the same cohort, the risk-prediction model indicated that 34 occurrences of diabetes could be avoided over 5 years, corresponding to a RW cost savings of €56.86 per patient and a total saving of approximately €1,933.24. These savings reflect avoided costs in treating adverse metabolic events and comparable costs in the acquisition of aripiprazole.Conclusions
Maintenance aripiprazole therapy offers medical and economic benefits over olanzapine, reflected by reduced incidence of metabolic syndrome and diabetes and associated lower costs. 相似文献998.
Aridon P Ragonese P De Fusco M Salemi G Casari G Savettieri G 《Parkinsonism & related disorders》2008,14(1):15-18
Familial essential tremor (FET) is a common hereditary movement disorder with phenotypic variability and genetic heterogeneity. To date, linkage analyses revealed three loci associated to essential tremor (ET) (ETM1 on 3q13, ETM2 on 2p22-25, and a locus on 6p23). We performed a genetic analysis of these candidate chromosomal regions in a fifth-generation Italian kindred with autosomal-dominant ET. Of the 22 clinically evaluated family members, nine were affected by ET. The genetic study indicates that the ET in this family is not associated to any of the known ET loci. These findings support evidence of further genetic heterogeneity for such disease. 相似文献
999.
Madia F Striano P Di Bonaventura C de Falco A de Falco FA Manfredi M Casari G Striano S Minetti C Zara F 《Neurogenetics》2008,9(2):139-142
Benign adult familial myoclonic epilepsy (BAFME or FAME) is an autosomal dominant condition, characterized by shivering-like tremors of cortical origin, myoclonus, and epilepsy. Linkage to chromosomes 2p11.1-q12.2 and 8q23.1-q24.11 has been reported in Japanese and Italian families, respectively. We aimed to determine whether a common founder haplotype was shared by five BAFME families from southern Italy and attempted preliminary genotype-phenotype correlation analyses. Five Italian BAFME families were identified. One family has not been previously reported. DNA from 53 affected individuals was genotyped with highly polymorphic microsatellite markers spanning chromosomes 2p11.1-q12.2 and 8q23.1-q24.11. Multipoint linkage analysis was performed using LINKMAP 5.1 software assuming an autosomal dominant trait with 0.99 penetrance and frequency of 0.001. Significant linkage was found on chromosome 2p11.1-q12.2 and a maximum cumulative lod score of 18.5 was found for markers D2S2161 and D2S388. The haplotype "5332" of adjacent markers D2S388, D2S2216, D2S113, and D2S2175 segregates with the disease in all families indicating that the same mutation inherited from a common ancestor segregates in these families. Preliminary genotype-phenotype showed that patients carrying the disease haplotype show minor clinical differences, suggesting that expressivity of the founder mutation is not markedly influenced by other factors. The identification of causative mutations in BAFME requires an extensive and collaborative screening effort. 相似文献
1000.
Ferrero S Esposito F Biamonti M Bentivoglio G Ragni N 《Expert Review of Neurotherapeutics》2008,8(6):979-988
Myasthenia gravis (MG) affects women in the second and third decades of life, overlapping with the childbearing years. During pregnancy, the course of this disease is unpredictable; worsening of symptoms occurs more likely during the first half of pregnancy and postpartum. MG can be well managed during pregnancy with relatively safe and effective therapies. Cesarean section is recommended only for obstetric reasons; epidural anesthesia is advised to reduce physical and emotional stress. Anticholinesterase drugs are the mainstay of treatment, when MG symptoms are not satisfactorily controlled, corticosteroids, azathioprine and in some cases cyclosporin A may be used. Life-threatening conditions (e.g., respiratory insufficiency) may occur during pregnancy; therefore, intensive check-ups by a gynecologist and a neurologist are necessary. 相似文献