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1.
Achim Rosemann Adam Balen Brigitte Nerlich Christine Hauskeller Margaret Sleeboom‐Faulkner Sarah Hartley Xinqing Zhang Nick Lee 《The Hastings Center report》2019,49(3):30-42
A central problem for the international governance of heritable germline gene editing is that there are important differences in attitudes and values as well as ethical and health care considerations around the world. These differences are reflected in a complicated and diverse regulatory landscape. Several publications have discussed whether reproductive uses would be legally permissible in individual countries and whether clinical applications could emerge in the context of regulatory gaps and gray areas. Systematic comparative studies that explore issues related to the governance of this technology from different national and international perspectives are needed to address the lack of knowledge in this area. In this research report, we contribute to filling this gap by presenting views of stakeholders in the United Kingdom on challenges to the governance of heritable genome editing. We present findings from a multistakeholder study conducted in the United Kingdom between October 2016 and January 2018 and funded by the Wellcome Trust. This research included interviews, literature analysis, and a workshop. We involved leading U.K. scientists, in vitro fertilization clinicians, and representatives from regulatory bodies, patient organizations, and other civil societal organizations, as well as fertility companies. Part one of this article explores stakeholder perceptions of possible global developments in heritable genome editing and associated risks and governance challenges. Part two presents a range of policy options that were generated during the workshop in relation to the challenges discussed in part one. 相似文献
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Fabian Falkenstein Marco Gessi Daniela Kandels Ho-Keung Ng René Schmidt Monika Warmuth-Metz Brigitte Bison Juergen Krauss Rolf-Dieter Kortmann Beate Timmermann Ulrich-Wilhelm Thomale Michael H. Albert Arnulf Pekrun Eberhard Maaß Astrid K. Gnekow Torsten Pietsch 《International journal of cancer. Journal international du cancer》2020,147(8):2159-2175
Reports on pediatric low-grade diffuse glioma WHO-grade II (DG2) suggest an impaired survival rate, but lack conclusive results for genetically defined DG2-entities. We analyzed the natural history, treatment and prognosis of DG2 and investigated which genetically defined sub-entities proved unfavorable for survival. Within the prospectively registered, population-based German/Swiss SIOP-LGG 2004 cohort 100 patients (age 0.8-17.8 years, 4% neurofibromatosis [NF1]) were diagnosed with a DG2. Following biopsy (41%) or variable extent of resection (59%), 65 patients received no adjuvant treatment. Radiologic progression or severe neurologic symptoms prompted chemotherapy (n = 18) or radiotherapy (n = 17). Multiple lines of salvage treatment were necessary for 19/35 patients. Five years event-free survival dropped to 0.44, while 5 years overall survival was 0.90 (median observation time 8.3 years). Extensive genetic profiling of 65/100 DG2 identified Histone3-K27M-mutation in 4, IDH1-mutation in 11, BRAF-V600-mutation in 12, KIAA1549-BRAF-fusions in 6 patients, while the remaining 32 tumor tissues did not show alterations of these genes. Progression to malignant glioma occurred in 12 cases of all genetically defined subgroups within a range of 0.5 to 10.8 years, except for tumors carrying KIAA1549-BRAF-fusions. Histone3-K27M-mutant tumors proved uniformly fatal within 0.6 to 2.4 years. The current LGG treatment strategy seems appropriate for all DG2-entities, with the exemption of Histone3-K27M-mutant tumors that require a HGG-related treatment strategy. Our data confirm the importance to genetically define pediatric low-grade diffuse gliomas for proper treatment decisions and risk assessment. 相似文献
3.
Zumel-Marne Angela Kundi Michael Castaño-Vinyals Gemma Alguacil Juan Petridou Eleni Th Georgakis Marios K. Morales-Suárez-Varela Maria Sadetzki Siegal Piro Sara Nagrani Rajini Filippini Graziella Hutter Hans-Peter Dikshit Rajesh Woehrer Adelheid Maule Milena Weinmann Tobias Krewski Daniel ′t Mannetje Andrea Momoli Franco Lacour Brigitte Mattioli Stefano Spinelli John J. Ritvo Paul Remen Thomas Kojimahara Noriko Eng Amanda Thurston Angela Lim Hyungryul Ha Mina Yamaguchi Naohito Mohipp Charmaine Bouka Evdoxia Eastman Chelsea Vermeulen Roel Kromhout Hans Cardis Elisabeth 《Journal of neuro-oncology》2020,147(2):427-440
Journal of Neuro-Oncology - We used data from MOBI-Kids, a 14-country international collaborative case–control study of brain tumors (BTs), to study clinical characteristics of the tumors in... 相似文献
4.
Conall T. Morgan Brigitte Mueller Varsha Thakur Vitor Guerra Callaghan Jull Luc Mertens Mark Friedberg Fraser Golding Mike Seed Steven E.S. Miner Edgar T. Jaeggi Cedric Manlhiot Lynne E. Nield 《The Canadian journal of cardiology》2019,35(4):453-461
Background
The purpose of the study was to evaluate the association between fetal echocardiographic measurements and the need for intervention (primary coarctation repair, staged coarctation repair, or catheter intervention) in prenatally diagnosed coarctation of the aorta.Methods
A single-centre retrospective cohort study (2005-2015) of 107 fetuses diagnosed with suspected coarctation of the aorta in the setting of an apex-forming left ventricle and antegrade flow across the mitral and aortic valves.Results
Median gestational age at diagnosis was 32 weeks (interquartile range, 23-35 weeks). Fifty-six (52%) did not require any neonatal intervention, 51 patients (48%) underwent a biventricular repair. In univariable analysis, an increase in ascending aorta (AAo) peak Doppler flow velocity (odds ratio [OR], 1.40 [95% confidence interval [CI], 1.05-1.91] per 20 cm/s; P = 0.03) was associated with intervention. No intervention was associated with larger isthmus size (OR, 0.23; P < 0.001), transverse arch diameter (OR, 0.23; P < 0.001), and aortic (OR, 0.72; P = 0.02), mitral (OR, 0.58; P = 0.001), and AAo (OR, 0.53; P < 0.001) z-scores. In multivariable analysis, higher peak AAo Doppler (OR, 2.51 [95% CI, 1.54-4.58] per 20 cm/s; P = 0.001) and younger gestational age at diagnosis (OR, 0.81 [95% CI, 0.70-0.93] per week; P = 0.005) were associated with intervention, whereas a higher AAo z-score (OR, 0.65 [95% CI, 0.43-0.94] per z; P = 0.029) and transverse arch dimension (OR, 0.44 [95% CI, 0.18-0.97]; P = 0.05) decreased the risk of intervention.Conclusions
In prenatally suspected coarctation, the variables associated with intervention comprised smaller AAo and transverse arch size, earlier gestational age at diagnosis, and the additional finding of a higher peak AAo Doppler. 相似文献5.
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