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101.
Hammond TG Carlsson L Davis AS Lynch WG MacKenzie I Redfern WS Sullivan AT Camm AJ 《Cardiovascular research》2001,49(4):741-750
OBJECTIVE: To assess current practice in the pharmaceutical industry for assessing the potential for QT interval prolongation by non-cardiovascular medicinal products. METHODS: The survey was based on responses from the Toxicology and (Safety) Pharmacology laboratories (a total of 74 laboratories) of 54 companies based in Europe, Japan/Asia and the USA, received between January and March 1999. RESULTS: All 54 companies conducted preclinical in vivo electrocardiography (EGG) evaluation of new active substances (NASs). Thirty of these companies also conducted in vitro cardiac electrophysiology studies on their compounds. The majority of in vivo work was done in conscious beagle dogs. There was no consistency within the industry in defining the magnitude of change in QT interval that is considered biologically important. Most companies considered a change greater than 10% to be important, although the design of the studies suggested that group sizes used may not give sufficient statistical power to detect this size of change. Bazett's formula was used by 41% of laboratories to correct QT for changes in heart rate, despite the fact that this formula is generally deemed to be unsuitable for use in dogs. For studies in anaesthetised dogs, the majority of laboratories used barbiturate anaesthesia, but researchers should be aware of the effects of this and some other anaesthetic agents on QT interval. As for in vitro cardiac electrophysiology, there was wide diversity in the testing methodologies, particularly with regard to the test species and tissue type. As with QT prolongation, there was no consensus on the degree of action potential prolongation to cause concern. For both in vitro and in vivo testing, the majority of companies tested a minimum of three dose (or concentration) levels in order to ascertain any dose-response relationship. CONCLUSIONS: The survey provides a snapshot of the practice in the industry prior to any internationally-agreed consensus on the most effective and efficient approaches to minimising the risk of QT prolongation by new drugs in man. It must be stated that for any given methodology, the 'majority view' in the industry is not necessarily best practice. 相似文献
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Hemostatic defects in dysproteinemias 总被引:7,自引:0,他引:7
105.
J Haapaniemi R Gadowski M Naini H Green D MacKenzie M Rubenfire 《Catheterization and cardiovascular diagnosis》1979,5(2):151-157
Hemoptysis is an unusual complication of flow-directed (Swan-Ganz) catheters. Over-inflation of the balloon with a shearing-induced rupture of a small pulmonary artery, and the spear effect of the catheter tip appear to be the mechanisms in the two cases presented. Diligent care to avoid overinflation of the balloon in the pulmonary capillary wedge position by observation of the pressure waveform is critical. The spear effect that is frequently seen during insertion may be eliminated by deflating the balloon at the first appearance of the pulmonary artery waveform and gradual advancement of the catheter five to eight cm, when the balloon is then reinflated to obtain the wedge. 相似文献
106.
NA Hanchard DR Murdock PL Magoulas M Bainbridge D Muzny YQ Wu M Wang AL McGuire JR Lupski RA Gibbs CW Brown 《Clinical genetics》2013,83(5):457-461
The advent of whole‐exome next‐generation sequencing (WES) has been pivotal for the molecular characterization of Mendelian disease; however, the clinical applicability of WES has remained relatively unexplored. We describe our exploration of WES as a diagnostic tool in a 3½‐year old female patient with a 2‐year history of episodic muscle weakness and paroxysmal dystonia who presented following a previous extensive but unrevealing diagnostic work‐up. WES was performed on the proband and her two parents. Parental exome data was used to filter potential de novo genomic events in the proband and suspected variants were confirmed using di‐deoxy sequencing. WES revealed a de novo non‐synonymous mutation in exon 21 of the calcium channel gene CACNA1S that has been previously reported in a single patient as a rare cause of atypical hypokalemic periodic paralysis. This was unexpected, as the proband's original differential diagnosis had included hypokalemic periodic paralysis, but clinical and laboratory features were equivocal, and standard clinical molecular testing for hypokalemic periodic paralysis and related disorders was negative. This report highlights the potential diagnostic utility of WES in clinical practice, with implications for the approach to similar diagnostic dilemmas in the future. 相似文献
107.
MacKenzie Megan Daviskiba Sydney Dow Miriam Johnston Peyton Balon Richard Javanbakht Arash Arfken Cynthia L. 《The Psychiatric quarterly》2021,92(3):1011-1020
Psychiatric Quarterly - Both healthcare workers (HCWs) and psychiatric patients during the COVID-19 pandemic appear to have elevated prevalence of psychiatric symptoms, but little is known about... 相似文献
108.
A. A. Belogurov JR. T. A. Zargarova V. I. Turobov N. I. Novikova O. O. Favorova N. A. Ponomarenko 《Autoimmunity》2013,46(4):362-364
Previously, we demonstrated that autoantibodies (AAb) in multiple sclerosis (MS) reveal site-specific binding and cleavage toward myelin basic protein (MBP) epitope library. We have found several fragments of MBP immunodominant in terms of AAb binding. Here, we applied these peptides to DA rats with induced protracted relapsing experimental allergic encephalomyelitis (EAE) most closely related to MS. DA rats with EAE induced by syngenic spinal cord homogenate in complete Freund's adjuvant were treated by nasal route with human MBP 46–62, 81–102, 124–139, 147–170, and Copaxone®. MBP 124–139 and 147–170 displayed only mild therapeutic effects but MBP 46–62 significantly reduced EAE, reflected by lower clinical scores and shorter EAE duration compared to controls. 相似文献
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Long‐term effectiveness of recommended boosted protease inhibitor‐based antiretroviral therapy in Europe 下载免费PDF全文
JR Santos A Cozzi‐Lepri A Phillips S De Wit C Pedersen P Reiss A Blaxhult A Lazzarin M Sluzhynska C Orkin C Duvivier J Bogner P Gargalianos‐Kakolyris P Schmid G Hassoun I Khromova M Beniowski V Hadziosmanovic D Sedlacek R Paredes JD Lundgren 《HIV medicine》2018,19(5):324-338