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101.
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Leopold Sellner Fuli Fan Nicola Giesen Maria-Luisa Schubert Hartmut Goldschmidt Carsten Müller-Tidow Peter Dreger Marc S. Raab Michael Schmitt 《International journal of cancer. Journal international du cancer》2020,147(8):2029-2041
Despite major advances in the treatment of multiple myeloma (MM), it remains a largely incurable disease with long-term control often dependent on continuous therapy. More effective, better tolerated treatments are therefore required to achieve durable remissions and to improve the quality of life of MM patients. Adoptive immunotherapy employing T cells expressing chimeric antigen receptors (CAR) is currently among the most promising treatment approaches in cancer. Within the target portfolio for MM immunotherapy, B-cell maturation antigen (BCMA) is among the most widely studied target antigens. BCMA is consistently expressed on MM cells and, importantly, is not expressed in critical healthy tissue. For this reason, it is an ideal target for MM immunotherapy. Several clinical trials evaluating different BCMA-targeting CAR constructs have been initiated and early results are very promising. However, in this rapidly developing clinical landscape, the ultimate role of BCMA-specific CAR-T cell therapy remains unclear. In this review, we will summarize currently available clinical data on BCMA-directed CAR-T cells and discuss potential future perspective for this promising treatment approach in MM. 相似文献
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Priya S. Shankarappa Cody J. Peer Arman Odabas Cynthia L. McCully Rafael C. Garcia William D. Figg Katherine E. Warren 《Cancer chemotherapy and pharmacology》2020,85(5):1003-1007
Pexidartinib (PLX3397) is a colony-stimulating factor-1 receptor (CSF-1R) inhibitor under clinical evaluation for potential CNS tumor treatment. This study aims to evaluate plasma pharmacokinetic parameters and estimate CNS penetrance of pexidartinib in a non-human primate (NHP) cerebrospinal fluid (CSF) reservoir model. Five male rhesus macaques, each with a previously implanted subcutaneous CSF ventricular reservoir and central venous lines, were used. NHPs received a single dose of 40 mg/kg pexidartinib (human equivalent dose of 800 mg/m2), administered orally as 200 mg tablets. Serial paired samples of blood and CSF were collected at 0–8, 24, 48, and 72 h. Pexidartinib concentrations were assayed by Integrated Analytical Solutions, Inc. (Berkeley, CA, USA) using HPLC/MS/MS. Pharmacokinetic (PK) analysis was performed using noncompartmental methods. Samples from four NHPs were evaluable. Average (± SD) plasma PK parameters were as follows: Cmax = 16.50 (± 6.67) μg/mL; Tmax = 5.00 (± 2.58) h; AUClast = 250.25 (± 103.76) h*μg/mL; CL = 0.18 (± 0.10) L/h/kg. In CSF, pexidartinib was either quantifiable (n = 2), with Cmax values of 16.1 and 10.1 ng/mL achieved 2–4 h after plasma Tmax, or undetected at all time points (n = 2, LLOQCSF = 5 ng/mL). Pexidartinib was well-tolerated in NHPs, with no Grade 3 or Grade 4 toxicities. The CSF penetration of pexidartinib after single-dose oral administration to NHPs was limited. 相似文献
105.
Samir Gupta MD MSCS Gloria D. Coronado PhD Keith Argenbright MD Alison T. Brenner PhD MPH Sheila F. Castañeda PhD Jason A. Dominitz MD MHS Beverly Green MD MPH Rachel B. Issaka MD MAS Theodore R. Levin MD Daniel S. Reuland MD MPH Lisa C. Richardson MD MPH Douglas J. Robertson MD MPH Amit G. Singal MD MS Michael Pignone MD MPH 《CA: a cancer journal for clinicians》2020,70(4):283-298
Uptake of colorectal cancer screening remains suboptimal. Mailed fecal immunochemical testing (FIT) offers promise for increasing screening rates, but optimal strategies for implementation have not been well synthesized. In June 2019, the Centers for Disease Control and Prevention convened a meeting of subject matter experts and stakeholders to answer key questions regarding mailed FIT implementation in the United States. Points of agreement included: 1) primers, such as texts, telephone calls, and printed mailings before mailed FIT, appear to contribute to effectiveness; 2) invitation letters should be brief and easy to read, and the signatory should be tailored based on setting; 3) instructions for FIT completion should be simple and address challenges that may lead to failed laboratory processing, such as notation of collection date; 4) reminders delivered to initial noncompleters should be used to increase the FIT return rate; 5) data infrastructure should identify eligible patients and track each step in the outreach process, from primer delivery through abnormal FIT follow-up; 6) protocols and procedures such as navigation should be in place to promote colonoscopy after abnormal FIT; 7) a high-quality, 1-sample FIT should be used; 8) sustainability requires a program champion and organizational support for the work, including sufficient funding and external policies (such as quality reporting requirements) to drive commitment to program investment; and 9) the cost effectiveness of mailed FIT has been established. Participants concluded that mailed FIT is an effective and efficient strategy with great potential for increasing colorectal cancer screening in diverse health care settings if more widely implemented. 相似文献
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Clinical and Translational Oncology - The specific association between PTEN deletion or ERG rearrangement and the recurrence of prostate cancer (PC) treated with radical prostatectomy (RP) or... 相似文献
108.
Anne‐Grete Mrtson Anette Veringa Edwin R. van den Heuvel Martijn Bakker Daan J. Touw Tjip S. van der Werf Lambert F. R. Span Jan‐Willem C. Alffenaar 《Mycoses》2019,62(8):698-705
Posaconazole is indicated for prophylaxis and treatment of invasive aspergillosis. Therapeutic drug monitoring (TDM) of posaconazole is used to optimise drug exposure. The aim of this study was to analyse and describe the TDM practices and exposure of posaconazole tablets. Patients who received posaconazole for treatment or prophylaxis of fungal infections were included in the study. The following therapeutic window was defined: if concentration was low (<0.7 mg/L for prophylaxis or < 1.5 mg/L for treatment) or high (>3.75 mg/L), the hospital pharmacist provided the physician with dosage advice, which implementation to patient care was analysed. A longitudinal analysis was performed to analyse if different confounding variables had an effect on posaconazole concentrations. Forty‐seven patients were enrolled resulting in 217 posaconazole trough concentrations. A median of 3 (IQR 1‐7) samples was measured per patient. The median concentration was 1.7 mg/L (IQR 0.8‐2.7) for prophylaxis and 1.76 mg/L (IQR 1.3‐2.3) for treatment. Overall, 78 posaconazole concentrations were out of the therapeutic window. For 45 (54%) of these concentrations, a dosage change was recommended. In the longitudinal analysis, the laboratory markers and patient baseline variables did not have an effect on posaconazole concentrations. Adequate posaconazole exposure was shown in 64% (affected 28 patients) of the measured concentrations. TDM practice of posaconazole can be improved by increasing the implementation rate of dose recommendation by a multidisciplinary antifungal stewardship team. 相似文献
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L.M. Abbassi M. Laurans A. Gasnier A. Smulevici H. Tournat J.-E. Bibault A. Huertas E. Jouglar A. Suissa S. Kreps P. Giraud C. Durdux 《Cancer radiothérapie》2019,23(4):316-321
PurposeTo evaluate prospectively asthenia and the quality of life in patients treated by stereotactic body irradiation and to determine their predictive factors.Methods and materialsQuality of life was assessed by the EORTC QLQ-C30 and asthenia was evaluated with the Brief Fatigue Inventory (BFI), on the first day (T1), last day (T2) and 1–3 weeks after the end of treatment (T3).ResultsSixty-three patients were treated with stereotactic body irradiation from February 2017 to May 2017 and 41 were included in the analysis (22 patients excluded for lack of understanding, organization, psychologic disorders or refusal). The mean number of fractions was 5 (± 2). The compliance to quality of life assessment was 98%, 95% was 81% at T1, T2 and T3, respectively. An increase of asthenia and a worsened quality of life were found in 12 (29%) and 14 (34%) patients between T1 and T2. Univariate analysis demonstrated a correlation between asthenia and quality of life were correlated with performans status (P = 0.03 and 0.05 respectively), hemoglobin level (p = 0.01 and 0.004), albumin level (P = 0.01 and 0.06), distance between home and radiotherapy department (P = 0.05 and 0.02). Multivariate analysis demonstrated a correlation between female gender (P = 0.012), albumin level (P < 0.001), distance over 25 km (P < 0.001) with asthenia, and albumin level (P = 0.003), hemoglobin level (P = 0.004) and previous chemotherapy (P = 0.003) with quality of life. No influence of stereotactic body ratiotherapy parameters was seen.ConclusionDespite hypofractionation, stereotactic body radiotherapy induced asthenia and deterioration of quality of life. 相似文献