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51.
Fraser L. Macrae Barnaby Peacock-Young Polly Bowman Stephen R. Baker Sam Quested Emma Linton Peter Hillmen Morag Griffin Talha Munir Daniel Payne Claire McKinley Deborah Clarke Darren J Newton Anita Hill Robert A. S. Ariëns 《American journal of hematology》2020,95(8):944-952
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare hematological disorder, characterized by complement-mediated intravascular hemolysis and thrombosis. The increased incidence of PNH-driven thrombosis is still poorly understood, but unlike other thrombotic disorders, is thought to largely occur through complement-mediated mechanisms. Treatment with a C5 inhibitor, eculizumab, has been shown to significantly reduce the number of thromboembolic events in these patients. Based on previously described links between changes in fibrin clot structure and thrombosis in other disorders, our aim was to investigate clot structure as a possible mechanism of thrombosis in patients with PNH and the anti-thrombotic effects of eculizumab treatment on clot structure. Clot structure, fibrinogen levels and thrombin generation were examined in plasma samples from 82 patients from the National PNH Service in Leeds, UK. Untreated PNH patients were found to have increased levels of fibrinogen and thrombin generation, with subsequent prothrombotic changes in clot structure. No link was found between increasing disease severity and fibrinogen levels, thrombin generation, clot formation or structure. However, eculizumab treated patients showed decreased fibrinogen levels, thrombin generation and clot density, with increasing time spent on treatment augmenting these antithrombotic effects. These data suggest that PNH patients have a prothrombotic clot phenotype due to increased fibrinogen levels and thrombin generation, and that the antithrombotic effects of eculizumab are, in-part, due to reductions in fibrinogen and thrombin generation with downstream effects on clot structure. 相似文献
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Sodium valproate is one of the most commonly used drugs to treat epilepsy. However, there is growing evidence that valproate can cause renal tubular injury in children, and there are increasing reports of valproate-induced Fanconi’s syndrome where the renal tubules lose their ability to reabsorb electrolytes, urea, glucose and protein. In this review article we attempt to bring together all of the studies conducted to date on the effects of valproate on renal function in epileptic children. The research is generally considered in two themes; the first comprises studies which indicate subclinical tubular injury measured by renal enzymes such as N-acetyl-β-D-glucosaminidase (NAG), and the second comprises clinical reports where Fanconi’s syndrome has occurred. This article goes on to analyse the current data and draws on recurring patterns to suggest that a specific subpopulation of severely disabled epileptic children may benefit hugely from the close monitoring of enzymes which are indicative of renal tubular injury, particularly NAG or in the very least periodical urinalysis. 相似文献
54.
Helminth parasites are highly successful pathogens, chronically infecting a quarter of the world's population, causing significant morbidity but rarely causing death. Protective immunity and expulsion of helminths is mediated by T-helper 2 (Th2) cells, type 2 (M2) macrophages, type 2 innate lymphoid cells, and eosinophils. Failure to mount these type 2 immune responses can result in immunopathology mediated by Th1 or Th17 cells. Helminths have evolved a wide variety of approaches for immune suppression, especially the generation of regulatory T cells and anti-inflammatory cytokines interleukin-10 and transforming growth factor-β. This is a very effective strategy for subverting protective immune responses to prolong their survival in the host but has the bystander effect of modulating immune responses to unrelated antigens. Epidemiological studies in humans have shown that infection with helminth parasites is associated with a low incidence of allergy/asthma and autoimmunity in developing countries. Experimental studies in mice have demonstrated that regulatory immune responses induced by helminth can suppress Th2 and Th1/Th17 responses that mediate allergy and autoimmunity, respectively. This has provided a rational explanation of the ‘hygiene hypothesis’ and has also led to the exploitation of helminths or their immunomodulatory products in the development of new immunosuppressive therapies for inflammatory diseases in humans. 相似文献
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Audrey E. Evans James R. Anderson Ilene B. Lefkowitz-Boudreaux Jonathan L. Finlay 《Pediatric blood & cancer》1996,27(1):8-14
In 1975, members of The Childrens Cancer Group (CCG) initiated a trial for patients with infratentorial medulloblastomas and ependymomas. Patients, all of whom received post-operative cranio-spinal irradiation (CSI), were randomized to receive or not receive adjuvant chemotherapy (CT) with lomustine (CCNU), vincristine, and prednisone for 1 year. Thirty-six of the 42 patients with ependymoma entered on study were suitable for analysis; 22 received combined modality therapy and 14 irradiation (RT) alone. The failure-free survival (FFS) for the entire sample at 10 years is 36% and overall survival (OS) 39%, with no difference in outcomes between the two regimens. Survival was better for females (73%) than males (21%) and for those older than 10 years (51% vs. 31%). There were two toxic deaths in the group receiving CT. We conclude from this study with long-term follow-up that the CT used was not effective in improving the outcome in children with ependymoma. © 1996 Wiley-Liss, Inc. 相似文献
57.
Rupa Narayan MD Traci M. Blonquist MS Ashkan Emadi MD PhD Robert P. Hasserjian MD Meghan Burke BS Christopher Lescinskas BS Donna S. Neuberg ScD Andrew M. Brunner MD Gabriela Hobbs MD Hanno Hock MD PhD Steven L. McAfee MD Yi-Bin Chen MD Eyal Attar MD Timothy A. Graubert MD Christina Bertoli MSN Jenna A. Moran MSN Meghan K. Bergeron MSN Julia E. Foster MSN Aura Y. Ramos BSN Tina T. Som BSN Megan K. Vartanian BSN RN Jennifer L. Story LPN Kristin McGregor MS Molly Macrae BS Tanya Behnan BS Margaret C. Wey PhD Jessica Rae BSN Frederic I. Preffer PhD Patricia Lesho BA Vu H. Duong MD Mason L. Mann BA Karen K. Ballen MD Christine Connolly BS Philip C. Amrein MD Amir T. Fathi MD 《Cancer》2020,126(6):1264-1273
58.
Samir Gupta MD MDCS AGAF Balambal Bharti MBBS MPH PhD Dennis J. Ahnen MD Daniel D. Buchanan PhD Iona C. Cheng PhD MPH Michelle Cotterchio PhD Jane C. Figueiredo PhD Steven J. Gallinger MD MSc Robert W. Haile DrPH MPH Mark A. Jenkins PhD Noralane M. Lindor MD Finlay A. Macrae MD AGAF Loïc Le Marchand MD PhD Polly A. Newcomb PhD MPH Stephen N. Thibodeau PhD Aung Ko Win MBBS MPH PhD Maria Elena Martinez PhD 《Cancer》2020,126(13):3013-3020
59.
Jennifer L. Beebe-Dimmer MPH PhD Julie J. Ruterbusch MPH Felicity W. K. Harper PhD Tara M. Baird MS David G. Finlay BS Andrew G. Rundle MPH DrPH Stephanie S. Pandolfi PhD Theresa A. Hastert PhD Kendra L. Schwartz MD Gerold Bepler MD Michael S. Simon MD Julia Mantey MPH Judy Abrams PhD Teri L. Albrecht PhD Ann G. Schwartz MPH PhD 《Cancer》2020,126(9):1987-1994
60.
NSF workshop report: Discovering general principles of nervous system organization by comparing brain maps across species 下载免费PDF全文
Georg F. Striedter T. Grant Belgard Chun‐Chun Chen Fred P. Davis Barbara L. Finlay Onur Güntürkün Melina E. Hale Julie A. Harris Erin E. Hecht Patrick R. Hof Hans A. Hofmann Linda Z. Holland Andrew N. Iwaniuk Erich D. Jarvis Harvey J. Karten Paul S. Katz William B. Kristan Eduardo R. Macagno Partha P. Mitra Leonid L. Moroz Todd M. Preuss Clifton W. Ragsdale Chet C. Sherwood Charles F. Stevens Maik C. Stüttgen Tadaharu Tsumoto Walter Wilczynski 《The Journal of comparative neurology》2014,522(7):1445-1453
Efforts to understand nervous system structure and function have received new impetus from the federal Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative. Comparative analyses can contribute to this effort by leading to the discovery of general principles of neural circuit design, information processing, and gene‐structure‐function relationships that are not apparent from studies on single species. We here propose to extend the comparative approach to nervous system ‘maps' comprising molecular, anatomical, and physiological data. This research will identify which neural features are likely to generalize across species, and which are unlikely to be broadly conserved. It will also suggest causal relationships between genes, development, adult anatomy, physiology, and, ultimately, behavior. These causal hypotheses can then be tested experimentally. Finally, insights from comparative research can inspire and guide technological development. To promote this research agenda, we recommend that teams of investigators coalesce around specific research questions and select a set of ‘reference species' to anchor their comparative analyses. These reference species should be chosen not just for practical advantages, but also with regard for their phylogenetic position, behavioral repertoire, well‐annotated genome, or other strategic reasons. We envision that the nervous systems of these reference species will be mapped in more detail than those of other species. The collected data may range from the molecular to the behavioral, depending on the research question. To integrate across levels of analysis and across species, standards for data collection, annotation, archiving, and distribution must be developed and respected. To that end, it will help to form networks or consortia of researchers and centers for science, technology, and education that focus on organized data collection, distribution, and training. These activities could be supported, at least in part, through existing mechanisms at NSF, NIH, and other agencies. It will also be important to develop new integrated software and database systems for cross‐species data analyses. Multidisciplinary efforts to develop such analytical tools should be supported financially. Finally, training opportunities should be created to stimulate multidisciplinary, integrative research into brain structure, function, and evolution. J. Comp. Neurol. 522:1445–1453, 2014. © 2014 Wiley Periodicals, Inc. 相似文献