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排序方式: 共有459条查询结果,搜索用时 15 毫秒
81.
UA Matulonis S Sharma S Ghamande MS Gordon SA Del Prete I Ray-Coquard E Kutarska H Liu H Fingert X Zhou H Danaee RJ Schilder 《Gynecologic oncology》2012,127(1):63-69
ObjectivesAurora A kinase (AAK), a key mitotic regulator, is implicated in the pathogenesis of several tumors, including ovarian cancer. This single-arm phase II study assessed single-agent efficacy and safety of the investigational AAK inhibitor MLN8237 (alisertib), in patients with platinum-refractory or ‐resistant epithelial ovarian, fallopian tube, or primary peritoneal carcinoma.MethodsAdult women with malignant, platinum-treated disease received MLN8237 50 mg orally twice daily for 7 days plus 14 days' rest (21-day cycles). The primary endpoint was combined objective tumor response rate per Response Evaluation Criteria in Solid Tumors (RECIST) and/or CA-125 criteria. Secondary endpoints included response duration, clinical benefit rate, progression-free survival (PFS), time-to-progression (TTP), and safety.ResultsThirty-one patients with epithelial ovarian (n = 25), primary peritoneal (n = 5), and fallopian tube carcinomas (n = 1) were enrolled. Responses of 6.9–11.1 month duration were observed in 3 (10%) patients with platinum-resistant ovarian cancer. Sixteen (52%) patients achieved stable disease with a mean duration of response of 2.86 months and which was durable for ≥ 3 months in 6 (19%). Median PFS and TTP were 1.9 months. Most common drug-related grade ≥ 3 adverse events were neutropenia (42%), leukopenia (23%), stomatitis, and thrombocytopenia (each 19%); 6% reported febrile neutropenia.ConclusionsThese data suggest that MLN8237 has modest single-agent antitumor activity and may produce responses and durable disease control in some patients with platinum-resistant ovarian cancer. MLN8237 is currently undergoing evaluation in a phase I/II trial with paclitaxel in recurrent ovarian cancer. 相似文献
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Reduced skeletal muscle satellite cell number alters muscle morphology after chronic stretch but allows limited serial sarcomere addition 下载免费PDF全文
Matthew C. Kinney MD Sudarshan Dayanidhi PT PhD Peter B. Dykstra BS John J. McCarthy PhD Charlotte A. Peterson PhD Richard L. Lieber PhD 《Muscle & nerve》2017,55(3):384-392
Introduction: Muscles add sarcomeres in response to stretch, presumably to maintain optimal sarcomere length. Clinical evidence from patients with cerebral palsy, who have both decreased serial sarcomere number and reduced satellite cells (SCs), suggests a hypothesis that SCs may be involved in sarcomere addition. Methods: A transgenic Pax7‐DTA mouse model underwent conditional SC depletion, and their soleii were then stretch‐immobilized to assess the capacity for sarcomere addition. Muscle architecture, morphology, and extracellular matrix (ECM) changes were also evaluated. Results: Mice in the SC‐reduced group achieved normal serial sarcomere addition in response to stretch. However, muscle fiber cross‐sectional area was significantly smaller and was associated with hypertrophic ECM changes, consistent with fibrosis. Conclusions: While a reduced SC population does not hinder serial sarcomere addition, SCs play a role in muscle adaptation to chronic stretch that involves maintenance of both fiber cross‐sectional area and ECM structure. Muscle Nerve 55 : 384–392, 2017 相似文献
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General anaesthesia vs. conscious sedation for transfemoral aortic valve implantation: a single UK centre before‐and‐after study 下载免费PDF全文
L. F. Miles K. R. Joshi E. H. Ogilvie C. G. Densem A. A. Klein M. O'Sullivan G. Martinez C. D. Sudarshan Y. Abu‐Omar J. F. Irons 《Anaesthesia》2016,71(8):892-900
Reported data suggest that 99% of transfemoral, transcatheter aortic valve implantations in the UK are performed under general anaesthesia. This before‐and‐after study is the first UK comparison of conscious sedation vs. general anaesthesia for this procedure. Patients who underwent general anaesthesia received tracheal intubation, positive pressure ventilation, radial arterial and central venous access and urinary catheterisation. Anaesthesia was maintained with propofol or sevoflurane. Patients who received conscious sedation had a fascia iliaca and ilioinguinal nerve block and low‐dose remifentanil infusion, without invasive monitoring or urinary catheterisation. Recruitment took place between August 2012 and July 2015, with a 6‐month crossover period between November 2013 and June 2014. A total of 88 patients were analysed, evenly divided between the two groups. Patients receiving conscious sedation had a shorter anaesthetic time (mean (SD) 121 (28) min vs. 145 (41) min; p < 0.001) and recovery room time (110 (50) min vs. 155 (48) min; p = 0.001), lower requirement for inotropes (4.6% vs 81.8%; OR (95% CI) 0.1 (0.002–0.050); p < 0.001) and a lower incidence of malignant dysrhythmia (0% vs 11.4%; p = 0.020). Conscious sedation appears a feasible alternative to general anaesthesia for this procedure and is associated with a reduced requirement for inotropic support and improved efficiency. 相似文献
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Dnyaneshwar Purushottam Gholap Ramdas Huse Sudarshan Dipake Machhindra K. Lande 《RSC advances》2023,13(3):2090
In the present research article, we have developed solid heterogenous silica supported lanthanum trifluoroacetate and trichloroacetate as green Lewis acid catalysts. These catalysts were synthesized by a novel, simple, cheap, clean, and environment friendly method. The physicochemical properties of the prepared catalysts were well studied and characterized by sophisticated spectroscopic techniques such as FTIR, TGA, XRD, EDX, SEM, TEM and BET analysis. The catalyst was utilized in the synthesis of arylimidazole derivatives via green protocols under solvent-free conditions at 70 °C with a higher yield, mild reaction conditions and a short reaction time. The catalyst works superiorly in water as well as in various organic solvents as a reusable and easily recoverable catalyst.Silica supported lanthanum trifluoroacetate and trichloroacetate as green Lewis acid catalysts were developed by a novel, simple, cheap, and environment friendly method and utilized them in the synthesis of arylimidazole derivatives via one pot solvent-free approach. 相似文献
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Elianna A. Bier Scott H. Robertson Geoffry M. Schrank Craig Rackley Joseph G. Mammarappallil Sudarshan Rajagopal H. Page McAdams Bastiaan Driehuys 《NMR in biomedicine》2019,32(1)
The spectral parameters of hyperpolarized 129Xe exchanging between airspaces, interstitial barrier, and red blood cells (RBCs) are sensitive to pulmonary pathophysiology. This study sought to evaluate whether the dynamics of 129Xe spectroscopy provide additional insight, with particular focus on quantifying cardiogenic oscillations in the RBC resonance. 129Xe spectra were dynamically acquired in eight healthy volunteers and nine subjects with idiopathic pulmonary fibrosis (IPF). 129Xe FIDs were collected every 20 ms (TE = 0.932 ms, 512 points, dwell time = 32 μs, flip angle ≈ 20°) during a 16 s breathing maneuver. The FIDs were pre‐processed using the spectral improvement by Fourier thresholding technique (SIFT) and fit in the time domain to determine the airspace, interstitial barrier, and RBC spectral parameters. The RBC and gas resonances were fit to a Lorentzian lineshape, while the barrier was fit to a Voigt lineshape to account for its greater structural heterogeneity. For each complex resonance the amplitude, chemical shift, linewidth(s), and phase were calculated. The time‐averaged spectra confirmed that the RBC to barrier amplitude ratio (RBC:barrier ratio) and RBC chemical shift are both reduced in IPF subjects. Their temporal dynamics showed that all three 129Xe resonances are affected by the breathing maneuver. Most notably, several RBC spectral parameters exhibited prominent oscillations at the cardiac frequency, and their peak‐to‐peak variation differed between IPF subjects and healthy volunteers. In the IPF cohort, oscillations were more prominent in the RBC amplitude (16.8 ± 5.2 versus 9.7 ± 2.9%; P = 0.008), chemical shift (0.43 ± 0.33 versus 0.083 ± 0.05 ppm; P < 0.001), and phase (7.7 ± 5.6 versus 1.4 ± 0.8°; P < 0.001). Dynamic 129Xe spectroscopy is a simple and sensitive tool that probes the temporal variability of gas exchange and may prove useful in discerning the underlying causes of its impairment. 相似文献
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