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191.
Reisz RR Evans DC Roberts EM Sues HD Yates AM 《Proceedings of the National Academy of Sciences of the United States of America》2012,109(7):2428-2433
The extensive Early Jurassic continental strata of southern Africa have yielded an exceptional record of dinosaurs that includes scores of partial to complete skeletons of the sauropodomorph Massospondylus, ranging from embryos to large adults. In 1976 an incomplete egg clutch including in ovo embryos of this dinosaur, the oldest known example in the fossil record, was collected from a road-cut talus, but its exact provenance was uncertain. An excavation program at the site started in 2006 has yielded multiple in situ egg clutches, documenting the oldest known dinosaurian nesting site, predating other similar sites by more than 100 million years. The presence of numerous clutches of eggs, some of which contain embryonic remains, in at least four distinct horizons within a small area, provides the earliest known evidence of complex reproductive behavior including site fidelity and colonial nesting in a terrestrial vertebrate. Thus, fossil and sedimentological evidence from this nesting site provides empirical data on reproductive strategies in early dinosaurs. A temporally calibrated optimization of dinosaurian reproductive biology not only demonstrates the primary significance of the Massospondylus nesting site, but also provides additional insights into the initial stages of the evolutionary history of dinosaurs, including evidence that deposition of eggs in a tightly organized single layer in a nest evolved independently from brooding. 相似文献
192.
AJ Geall A Verma GR Otten CA Shaw A Hekele K Banerjee Y Cu CW Beard LA Brito T Krucker DT O'Hagan M Singh PW Mason NM Valiante PR Dormitzer SW Barnett R Rappuoli JB Ulmer CW Mandl 《Proceedings of the National Academy of Sciences of the United States of America》2012,109(36):14604-14609
Despite more than two decades of research and development on nucleic acid vaccines, there is still no commercial product for human use. Taking advantage of the recent innovations in systemic delivery of short interfering RNA (siRNA) using lipid nanoparticles (LNPs), we developed a self-amplifying RNA vaccine. Here we show that nonviral delivery of a 9-kb self-amplifying RNA encapsulated within an LNP substantially increased immunogenicity compared with delivery of unformulated RNA. This unique vaccine technology was found to elicit broad, potent, and protective immune responses, that were comparable to a viral delivery technology, but without the inherent limitations of viral vectors. Given the many positive attributes of nucleic acid vaccines, our results suggest that a comprehensive evaluation of nonviral technologies to deliver self-amplifying RNA vaccines is warranted. 相似文献
193.
Jacques Banchereau Sandra Zurawski LuAnn Thompson-Snipes Jean-Philippe Blanck Sandra Clayton Adiel Munk Yanying Cao Zhiqing Wang Sunaina Khandelwal Jiancheng Hu William H. McCoy IV Karolina A. Palucka Yoram Reiter Daved H. Fremont Gerard Zurawski Marco Colonna Andrey S. Shaw Eynav Klechevsky 《Proceedings of the National Academy of Sciences of the United States of America》2012,109(46):18885-18890
194.
195.
196.
Damman P Wallentin L Fox KA Windhausen F Hirsch A Clayton T Pocock SJ Lagerqvist B Tijssen JG de Winter RJ 《Circulation》2012,125(4):568-576
197.
Toze CL Dalal CB Nevill TJ Gillan TL Abou Mourad YR Barnett MJ Broady RC Forrest DL Hogge DE Nantel SH Power MM Song KW Sutherland HJ Smith CA Narayanan S Young SS Connors JM Shepherd JD 《British journal of haematology》2012,158(2):174-185
The curative potential of allogeneic haematopoietic stem cell transplant (allo HSCT) in chronic lymphocytic leukaemia CLL is established, with a demonstrated role for graft-versus-leukaemia and less certainty for other factors in determining outcome. The first two decades of CLL patients proceeding to allo HSCT at the Leukaemia/Bone Marrow Transplant Program of British Columbia (n = 49 consecutive, 1991-2009) were studied to clarify factors predicting outcome. The donor was related in 29 (59%) and unrelated in 20 (41%). Conditioning was reduced-intensity in 27 (55%) and myeloablative in 22 (45%). Thirty-one of 49 patients survive with median follow-up of 5 years (0·2-15). Cumulative incidence of non-relapse mortality; complete remission (CR); clearance of fluorescence in situ hybridization (FISH) abnormality and progression at 10 years was 36%; 69%; 55% and 22%. Overall survival (OS) was 63% at 2 years; 55% at 5 years and beyond. Factors predicting OS (P value by log rank <0·05) were: comorbidity index <3, FISH rank (Dohner) and 17p deletion, alemtuzumab pre-HSCT, achievement of CR post-HSCT, donor chimerism >90%, clearance of FISH abnormality post-HSCT and absence of high-grade (3-4) graft-versus-host disease. Results from this province-wide, two-decade cohort demonstrated that a substantial proportion of patients with high-risk CLL become long term disease-free survivors. 相似文献
198.
Ladan Kobari Frank Yates Noufissa Oudrhiri Alain Francina Laurent Kiger Christelle Mazurier Shaghayegh Rouzbeh Wassim El-Nemer Nicolas Hebert Marie-Catherine Giarratana Sabine Fran?ois Alain Chapel Hélène Lapillonne Dominique Luton Annelise Bennaceur-Griscelli Luc Douay 《Haematologica》2012,97(12):1795-1803
Background
Human induced pluripotent stem cells offer perspectives for cell therapy and research models for diseases. We applied this approach to the normal and pathological erythroid differentiation model by establishing induced pluripotent stem cells from normal and homozygous sickle cell disease donors.Design and Methods
We addressed the question as to whether these cells can reach complete erythroid terminal maturation notably with a complete switch from fetal to adult hemoglobin. Sickle cell disease induced pluripotent stem cells were differentiated in vitro into red blood cells and characterized for their terminal maturation in terms of hemoglobin content, oxygen transport capacity, deformability, sickling and adherence. Nucleated erythroblast populations generated from normal and pathological induced pluripotent stem cells were then injected into non-obese diabetic severe combined immunodeficiency mice to follow the in vivo hemoglobin maturation.Results
We observed that in vitro erythroid differentiation results in predominance of fetal hemoglobin which rescues the functionality of red blood cells in the pathological model of sickle cell disease. We observed, in vivo, the switch from fetal to adult hemoglobin after infusion of nucleated erythroid precursors derived from either normal or pathological induced pluripotent stem cells into mice.Conclusions
These results demonstrate that human induced pluripotent stem cells: i) can achieve complete terminal erythroid maturation, in vitro in terms of nucleus expulsion and in vivo in terms of hemoglobin maturation; and ii) open the way to generation of functionally corrected red blood cells from sickle cell disease induced pluripotent stem cells, without any genetic modification or drug treatment.Key words: human induced pluripotent stem cells, terminal maturation, erythropoietic differentiation 相似文献199.
Marcus Flather June-Wha Rhee Derek B. Boothroyd Eric Boersma Maria Mori Brooks Didier Carrié Tim C. Clayton Nicholas Danchin Christian W. Hamm Whady A. Hueb Spencer B. King Stuart J. Pocock Alfredo E. Rodriguez Patrick Serruys Ulrich Sigwart Rodney H. Stables Mark A. Hlatky 《Journal of the American College of Cardiology》2012
200.
Michelle L. O'Donoghue Ajay Vaidya Rizwan Afsal Joakim Alfredsson William E. Boden Eugene Braunwald Christopher P. Cannon Tim C. Clayton Robbert J. de Winter Keith A.A. Fox Bo Lagerqvist Peter A. McCullough Sabina A. Murphy Rudolf Spacek Eva Swahn Fons Windhausen Marc S. Sabatine 《Journal of the American College of Cardiology》2012