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991.
Theo Vermeire Tom Aldenberg Harrie Buist Sylvia Escher Inge Mangelsdorf Eduard Pauné Emiel Rorije Dinant Kroese 《Regulatory toxicology and pharmacology : RTP》2013
Chemical substances policies in Europe are aiming towards chemical safety and at the same time a reduction in animal testing. These goals are alleged to be reachable by mining as many relevant data as possible, evaluate these data with regard to validity, reliability and relevance, and use of these data in so-called Integrated Testing Strategies (ITS). 相似文献
992.
Philippe Huguelet Laurence Borras Christiane Gillieron Pierre-Yves Brandt Sylvia Mohr 《Substance use & misuse》2013,48(4):502-513
Substance misuse represents a major issue in the treatment of schizophrenia patients. Spirituality and religiousness have been shown to reduce substance misuse and to foster recovery among substance misusers in the general population. One hundred and fifteen stabilized outpatients with schizophrenia (mean age 39; 70% male) were selected in 2004 for an interview about religious coping. Religious involvement was significantly inversely correlated to substance use and abuse. A content analysis showed that religion may play a protective role toward substance misuse in 14% of the total sample, especially for patients who had stopped substance misuse (42%). It played a negative role in 3% of cases. Religion may play a role in the recovery of schizophrenia patients with substance misuse comorbidity. 相似文献
993.
Andrea Lunardi Kaitlyn A. Webster Antonella Papa Bhavik Padmani John G. Clohessy Roderick T. Bronson Pier Paolo Pandolfi 《Oncotarget》2014,5(4):894-900
The PI3K/AKT pathway governs a plethora of cellular processes, including cell growth, proliferation, and metabolism, in response to growth factors and cytokines. By acting as a unique lipid phosphatase converting phosphatidylinositol-3,4,5,-trisphosphate (PIP3) to phosphatidylinositol-4,5,-bisphosphate (PIP2), phosphatase and tensin homolog (PTEN) acts as the major cellular suppressor of PI3K signaling and AKT activation. Recently, PI3K mutations and loss/mutation of PTEN have been characterized in human gallbladder tumors; whether aberrant PTEN/PI3K pathway plays a causal role in gallbladder carcinogenesis, however, remains unknown. Herein we show that in mice, deregulation of PI3K/AKT signaling is sufficient to transform gallbladder epithelial cells and trigger fully penetrant, highly proliferative gallbladder tumors characterized by high levels of phospho-AKT. Histopathologically, these mouse tumors faithfully resemble human adenomatous gallbladder lesions. The identification of PI3K pathway deregulation as both an early event in the neoplastic transformation of the gallbladder epithelium and a main mechanism of tumor growth in Pten heterozygous and Pten mutant mouse models provides a new framework for studying in vivo the efficacy of target therapies directed against the PI3K pathway, as advanced metastatic tumors are often addicted to “trunkular” mutations. 相似文献
994.
995.
Mandeep Singh Yi Ding Li-Ying Zhang Dong Song Yun Gong Sylvia Adams Dara S Ross Jin-Hua Wang Shruti Grover Dinesh Chandra Doval Charles Shao Zi-Li He Victor Chang Warren W Chin Fang-Ming Deng Baljit Singh David Zhang Ru-Liang Xu Peng Lee 《American journal of cancer research》2014,4(4):337-352
Background: Racial disparities among breast cancer (BCa) patients are known but not well studied in early-onset BCa. We analyzed molecular subtypes in early-onset BCa across five major races. Methods: A total of 2120 cases were included from non-Hispanic White (NHW), African American (AA) and Hispanic, Chinese and Indian. Based on ER, PR and HER-2 status, BCa was classified into 4 intrinsic subtypes as Luminal A, Luminal B, HER2/neu overexpression and Triple negative BCa (TNBC) subtypes. Data was stratified according to race and age as younger/early-onset group (40-years and younger) and older group (50-years and older). Results: In early-onset BCa, incidence of TNBC was significantly higher (p = 0.0369) in Indian women followed by AA, Hispanic, NHW and Chinese women. Incidence of Her2 over-expression subtype also was highest in Indian women, followed by Hispanic, Chinese, AA and NHW women. In contrast, Luminal B subtype was most significantly higher in AA women (p = 0.0000) followed by NHW (p = 0.0002), Chinese (p = 0.0003), Hispanic (0.0128) and Indian (p = 0.0468) women. Luminal A subtype was most significantly reduced in Indian women (p = 0.0113) followed by Hispanic, AA, NHW and Chinese women. These results were based on statistical analysis with the mean of older group populations. Conclusions: These results show significant disparities in receptor subtypes across races. This study will contribute in developing optimal clinical trial protocols and personalized management strategies for early-onset BCa patients. 相似文献
996.
Martin Schuler Jürgen R. Fischer Christian Grohé Sylvia Gütz Michael Thomas Martin Kimmich Claus‐Peter Schneider Eckart Laack Angela Märten for the Afatinib Compassionate Use Consortium 《The oncologist》2014,19(10):1100-1109
Background.
Afatinib, an irreversible ErbB family blocker, demonstrated superiority to chemotherapy as first-line treatment in patients with EGFR-mutated non-small cell lung cancer (NSCLC). Afatinib is also active in patients progressing on EGFR tyrosine kinase inhibitors (EGFR-TKIs). We report the results of a large cohort of NSCLC patients receiving afatinib within a compassionate-use program (CUP).Patients and Methods.
Patients with advanced NSCLC progressing after one line or more of chemotherapy and one line or more of EGFR-TKI treatment with either an EGFR mutation or documented clinical benefit were enrolled. Data collection was not monitored or verified by central review. The intention of this CUP was to provide controlled preregistration access to afatinib for patients with life-threatening diseases and no other treatment option.Results.
From May 2010 to October 2013, 573 patients (65% female; median age: 64 years [range: 28–89 years]) were enrolled, with strong participation of community oncologists. Comorbidities were allowed, including second malignancies in 11% of patients. EGFR mutation status was available in 391 patients (72%), and 83% tested mutation positive. Median time to treatment failure (TTF) of 541 patients treated with afatinib was 3.7 months (range: 0.0 to >29.0 months). Median TTF was 4.0 and 2.7 months in patients with adenocarcinomas and squamous cell carcinomas, respectively, and 4.6 months in patients with EGFR-mutated NSCLC. Adverse events were generally manageable.Conclusion.
Afatinib was able to be given in a real-world setting to heavily pretreated patients with EGFR-mutated or EGFR-TKI-sensitive NSCLC. Acknowledging the constraints of data collection in a CUP, afatinib appears to be safe and to confer some clinical benefit in this population. 相似文献997.
Bruno Coudert Jean-Yves Pierga Marie-Ange Mouret-Reynier Kaldoun Kerrou Jean-Marc Ferrero Thierry Petit Pierre Kerbrat Pierre-François Dupré Thomas Bachelot Philippe Gabelle Sylvia Giard David Coeffic Philippe Bougnoux Jean-Briac Prevost Gilles Paintaud Gilles Thibault Juana Hernandez Mathieu Coudert Alina Berriolo-Riedinger 《The lancet oncology》2014,15(13):1493-1502
998.
Ulrich Matt Omar Sharif Rui Martins Tanja Furtner Lorene Langeberg Riem Gawish Immanuel Elbau Ana Zivkovic Karin Lakovits Olga Oskolkova Bianca Doninger Andreas Vychytil Thomas Perkmann Gernot Schabbauer Christoph J. Binder Valery N. Bochkov John D. Scott Sylvia Knapp 《The Journal of clinical investigation》2013,123(10):4540
999.
1000.
Brett Theeler MD Sylvia Lucas MD PhD Ronald G Riechers II MD Robert L Ruff MD PhD 《Headache》2013,53(6):881-900
Post‐traumatic headache (PTH) is the most frequent symptom after traumatic brain injury (TBI). We review the epidemiology and characterization of PTH in military and civilian settings. PTH appears to be more likely to develop following mild TBI (concussion) compared with moderate or severe TBI. PTH often clinically resembles primary headache disorders, usually migraine. For migraine‐like PTH, individuals who had the most severe headache pain had the highest headache frequencies. Based on studies to date in both civilian and military settings, we recommend changes to the current definition of PTH. Anxiety disorders such as post‐traumatic stress disorder (PTSD) are frequently associated with TBI, especially in military populations and in combat settings. PTSD can complicate treatment of PTH as a comorbid condition of post‐concussion syndrome. PTH should not be treated as an isolated condition. Comorbid conditions such as PTSD and sleep disturbances also need to be treated. Double‐blind placebo‐controlled trials in PTH population are necessary to see whether similar phenotypes in the primary headache disorders and PTH will respond similarly to treatment. Until blinded treatment trials are completed, we suggest that, when possible, PTH be treated as one would treat the primary headache disorder(s) that the PTH most closely resembles. 相似文献