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排序方式: 共有3238条查询结果,搜索用时 31 毫秒
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Espersen Caroline Modin Daniel Hoffmann Søren Hagemann Christoffer A. Hagemann Rikke A. Olsen Flemming J. Fritz-Hansen Thomas Platz Elke Møgelvang Rasmus Biering-Sørensen Tor 《The international journal of cardiovascular imaging》2022,38(1):131-140
The International Journal of Cardiovascular Imaging - Global longitudinal strain (GLS) has proven to be a powerful prognostic marker in various patient populations, but the prognostic value of... 相似文献
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Qingyang Xiao Yitian Zhou Stefan Winter Florian Büttner Elke Schaeffeler Matthias Schwab Volker M. Lauschke 《International journal of cancer. Journal international du cancer》2020,146(9):2475-2487
Multidrug resistance due to facilitated drug efflux mediated by ATP-binding cassette (ABC) transporters is a main cause for failure of cancer therapy. Genetic polymorphisms in ABC genes affect the disposition of chemotherapeutics and constitute important biomarkers for therapeutic response and toxicity. Here we correlated germline variability in ABC transporters with disease-specific survival (DSS) in 960 breast cancer (BRCA), 314 clear cell renal cell carcinoma and 325 hepatocellular carcinoma patients. We find that variant burden in ABCC1 is a strong predictor of DSS in BRCA patients, whereas candidate polymorphisms are not associated with DSS. This association is highly drug-specific for subgroups treated with the MRP1 substrates cyclophosphamide (log-rank p = 0.0011) and doxorubicin (log-rank p = 0.0088) independent of age and tumor stage, whereas no association was found in individuals treated with tamoxifen (log-rank p = 0.13). Structural mapping of significant variants revealed multiple variants at residues involved in protein stability, cofactor stabilization or substrate binding. Our results demonstrate that BRCA patients with high variant burden in ABCC1 are less prone to respond appropriately to pharmacological therapy with MRP1 substrates, thus incentivizing the consideration of genomic germline data for precision cancer medicine. 相似文献
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Testing association of rare genetic variants with resistance to three common antiseizure medications
Stefan Wolking Claudia Moreau Anne T. Nies Elke Schaeffeler Mark McCormack Pauls Auce Andreja Avbersek Felicitas Becker Martin Krenn Rikke S. Møller Marina Nikanorova Yvonne G. Weber Sarah Weckhuysen Gianpiero L. Cavalleri Norman Delanty Chantal Depondt Michael R. Johnson Bobby P.C. Koeleman Wolfram S. Kunz Anthony G. Marson Josemir W. Sander Graeme J. Sills Pasquale Striano Federico Zara Fritz Zimprich Matthias Schwab Roland Krause Sanjay M. Sisodiya Patrick Cossette Simon L. Girard Holger Lerche EpiPGX Consortium 《Epilepsia》2020,61(4):657-666
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Very preterm children are at increased risk of reduced processing speed at 5 years of age,predicted by typical complications of prematurity and prenatal smoking 下载免费PDF全文
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Ronald Niebecker Siv J?nsson Mats O. Karlsson Raymond Miller Joakim Nyberg Elke H. J. Krekels Ulrika S. H. Simonsson 《British journal of clinical pharmacology》2015,80(6):1374-1387
AimsThis study characterized the population pharmacokinetics of edoxaban in patients with symptomatic deep‐vein thrombosis and/or pulmonary embolism in the Hokusai‐VTE phase 3 study. The impact of the protocol‐specified 50% dose reductions applied to patients with body weight ≤ 60 kg, creatinine clearance (CLcr) of 30 to 50 ml min–1 or concomitant P‐glycoprotein inhibitor on edoxaban exposure was assessed using simulations.MethodsThe sparse data from Hokusai‐VTE, 9531 concentrations collected from 3707 patients, were pooled with data from 13 phase 1 studies. In the analysis, the covariate relationships used for dose reductions were estimated and differences between healthy subjects and patients as well as additional covariate effects of age, race and gender were explored based on statistical and clinical significance.ResultsA linear two‐compartment model with first order absorption preceded by a lag time best described the data. Allometrically scaled body weight was included on disposition parameters. Apparent clearance was parameterized as non‐renal and renal. The latter increased non‐linearly with increasing CLcr. Compared with healthy volunteers, inter‐compartmental clearance and the CLcr covariate effect were different in patients (+64.6% and +274%). Asian patients had a 22.6% increased apparent central volume of distribution. The effect of co‐administration of P‐glycoprotein inhibitors seen in phase 1 could not be confirmed in the phase 3 data. Model‐based simulations revealed lower exposure in dose‐reduced compared with non‐dose‐reduced patients.ConclusionsThe adopted dose‐reduction strategy resulted in reduced exposure compared with non‐dose‐reduced, thereby overcompensating for covariate effects. The clinical impact of these differences on safety and efficacy remains to be evaluated. 相似文献
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Walter Strobl Tim Theologis Reinald Brunner Serdar Kocer Elke Viehweger Ignacio Pascual-Pascual Richard Placzek 《Toxins》2015,7(5):1629-1648
Botulinum toxin A (BoNT-A) is considered a safe and effective therapy for children with cerebral palsy (CP), especially in the hands of experienced injectors and for the majority of children. Recently, some risks have been noted for children with Gross Motor Classification Scale (GMFCS) of IV and the risks are substantial for level V. Recommendations for treatment with BoNT-A have been published since 1993, with continuous optimisation and development of new treatment concepts. This leads to modifications in the clinical decision making process, indications, injection techniques, assessments, and evaluations. This article summarises the state of the art of BoNT-A treatment in children with CP, based mainly on the literature and expert opinions by an international paediatric orthopaedic user group. BoNT-A is an important part of multimodal management, to support motor development and improve function when the targeted management of spasticity in specific muscle groups is clinically indicated. Individualised assessment and treatment are essential, and should be part of an integrated approach chosen to support the achievement of motor milestones. To this end, goals should be set for both the long term and for each injection cycle. The correct choice of target muscles is also important; not all spastic muscles need to be injected. A more focused approach needs to be established to improve function and motor development, and to prevent adverse compensations and contractures. Furthermore, the timeline of BoNT-A treatment extends from infancy to adulthood, and treatment should take into account the change in indications with age. 相似文献
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Aßfalg Volker Hassiotis Sophia Radonjic Marion Göcmez Sarah Friess Helmut Frank Elke Königstorfer Jörg 《Bundesgesundheitsblatt, Gesundheitsforschung, Gesundheitsschutz》2022,65(3):348-356
Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz - Seit Oktober 2017 ist ein strukturiertes Entlassmanagement zur Überleitung von Patienten aus dem stationären in den... 相似文献