全文获取类型
收费全文 | 1090篇 |
免费 | 76篇 |
国内免费 | 7篇 |
专业分类
耳鼻咽喉 | 4篇 |
儿科学 | 21篇 |
妇产科学 | 24篇 |
基础医学 | 194篇 |
口腔科学 | 14篇 |
临床医学 | 92篇 |
内科学 | 215篇 |
皮肤病学 | 22篇 |
神经病学 | 117篇 |
特种医学 | 17篇 |
外科学 | 82篇 |
综合类 | 3篇 |
一般理论 | 2篇 |
预防医学 | 90篇 |
眼科学 | 13篇 |
药学 | 107篇 |
中国医学 | 1篇 |
肿瘤学 | 155篇 |
出版年
2024年 | 3篇 |
2023年 | 12篇 |
2022年 | 36篇 |
2021年 | 62篇 |
2020年 | 21篇 |
2019年 | 48篇 |
2018年 | 33篇 |
2017年 | 21篇 |
2016年 | 33篇 |
2015年 | 48篇 |
2014年 | 71篇 |
2013年 | 65篇 |
2012年 | 126篇 |
2011年 | 105篇 |
2010年 | 52篇 |
2009年 | 34篇 |
2008年 | 78篇 |
2007年 | 60篇 |
2006年 | 46篇 |
2005年 | 65篇 |
2004年 | 45篇 |
2003年 | 40篇 |
2002年 | 38篇 |
2001年 | 4篇 |
2000年 | 2篇 |
1999年 | 2篇 |
1998年 | 8篇 |
1997年 | 2篇 |
1996年 | 2篇 |
1995年 | 1篇 |
1993年 | 1篇 |
1992年 | 1篇 |
1991年 | 2篇 |
1988年 | 1篇 |
1984年 | 1篇 |
1981年 | 1篇 |
1974年 | 1篇 |
1973年 | 1篇 |
1970年 | 1篇 |
排序方式: 共有1173条查询结果,搜索用时 15 毫秒
21.
Tatiana Raskovalova Patrick B. Deegan Pramod K. Mistry Elena Pavlova Ruby Yang Ari Zimran Juliette Berger Celine Bourgne Bruno Pereira Jose Labarere Marc G. Berger 《Haematologica》2021,106(2):437
Chitotriosidase activity and CCL18 concentration are interchangeably used for monitoring Gaucher disease (GD) activity, together with clinical assessment. However, comparative studies of these two biomarkers are scarce and of limited sample size. The aim of this systematic review with meta-analysis of individual participant data (IPD) was to compare the accuracy of chitotriosidase activity and CCL18 concentration for assessing type I GD severity. We identified cross-sectional and prospective cohort studies by searching Medline, EMBASE, and CENTRAL from January 1995 to June 2017, and by contacting research groups. The primary outcome was a composite of liver volume >1.25 multiple of normal (MN), spleen volume >5 MN, hemoglobin concentration <11 g/dL, and platelet count <100x109/L. Overall, IPD included 1,109 observations from 334 patients enrolled in nine primary studies, after excluding 111 patients with undocumented values and 18 patients with deficient chitotriosidase activity. IPD were unavailable for 14 eligible primary studies. The primary outcome was associated with a 5.3-fold (95% Confidence Interval [CI]: 4.2-6.6) and 3.0-fold (95% CI: 2.6-3.6) increase of the geometric mean for chitotriosidase activity and CCL18 concentration, respectively. The corresponding areas under the receiver operating characteristics curves were 0.82 and 0.84 (summary difference, 0.02, 95% CI: -0.02 to 0.05). The addition of chitotriosidase activity did not improve the accuracy of the CCL18 concentration. Estimates remained robust in the sensitivity analysis and consistent across subgroups. Neither the chitotriosidase activity nor the CCL18 concentration varied significantly according to a recent history of bone events among 97 patients. In conclusion, the CCL18 concentration is as accurate as chitotriosidase activity in assessing hematological and visceral parameters of GD severity and can be measured in all GD patients. This meta-analysis supports the use of CCL18 rather than chitotriosidase activity for monito-ring GD activity in routine practice. 相似文献
22.
Cameron R. Stewart Anthony L. Keyburn Celine Deffrasnes S. Mark Tompkins 《Developmental and comparative immunology》2013
The importance of poultry, particularly chicken, as a food source continues to increase globally. Moreover, zoonotic infectious diseases such as avian influenza virus not only continue to impact poultry production, but also pose an increasing threat to public health. This review discusses the importance of poultry in both agricultural and public health arenas. Recent developments in avian immunology are described, with an emphasis on host–pathogen interactions and noting differences from mammalian systems. Next generation technologies including functional genomics and targeted gene disruption (e.g. zinc finger nucleases and meganucleases) are discussed as new approaches for not only understanding immune responses in poultry, but also as novel disease intervention strategies. 相似文献
23.
Hans H. Hirsch Piotr Kardas Denise Kranz Celine Leboeuf 《APMIS : acta pathologica, microbiologica, et immunologica Scandinavica》2013,121(8):685-727
JC polyomavirus (JCPyV) was the first of now 12 PyVs detected in humans, when in 1964, PyV particles were revealed by electron microscopy in progressive multifocal leukoencephalopathy (PML) tissues. JCPyV infection is common in 35–70% of the general population, and the virus thereafter persists in the renourinary tract. One third of healthy adults asymptomatically shed JCPyV at approximately 50 000 copies/mL urine. PML is rare having an incidence of <0.3 per 100 000 person years in the general population. This increased to 2.4 per 1000 person years in HIV‐AIDS patients without combination antiretroviral therapy (cART). Recently, PML emerged in multiple sclerosis patients treated with natalizumab to 2.13 cases per 1000 patients. Natalizumab blocks α4‐integrin‐dependent lymphocyte homing to the brain suggesting that not the overall cellular immunodeficiency but local failure of brain immune surveillance is a pivotal factor for PML. Recovering JCPyV‐specific immune control, e.g., by starting cART or discontinuing natalizumab, significantly improves PML survival, but is challenged by the immune reconstitution inflammatory syndrome. Important steps of PML pathogenesis are undefined, and antiviral therapies are lacking. New clues might come from molecular and functional profiling of JCPyV and PML pathology and comparison with other replicative pathologies such as granule cell neuronopathy and (meningo‐)encephalitis, and non‐replicative JCPyV pathology possibly contributing to some malignancies. Given the increasing number of immunologically vulnerable patients, a critical reappraisal of JCPyV infection, replication and disease seems warranted. 相似文献
24.
Christelle Dufour Stephanie Foulon Anne Geoffray Julien Masliah-Planchon Dominique Figarella-Branger Valerie Bernier-Chastagner Laetitia Padovani La Guerrini-Rousseau Cecile Faure-Conter Celine Icher Anne-Isabelle Bertozzi Pierre Leblond Tasnime Akbaraly Franck Bourdeaut Nicolas Andr Celine Chapp Pascale Schneider Emilie De Carli Pascal Chastagner Claire Berger Julien Lejeune Christine Soler Natacha Entz-Werl Marie-Bernadette Delisle 《Neuro-oncology》2021,23(7):1163
BackgroundHigh-risk medulloblastoma is defined by the presence of metastatic disease and/or incomplete resection and/or unfavorable histopathology and/or tumors with MYC amplification. We aimed to assess the 3-year progression-free survival (PFS) and define the molecular characteristics associated with PFS in patients aged 5–19 years with newly diagnosed high-risk medulloblastoma treated according to the phase II trial PNET HR+5.MethodsAll children received postoperative induction chemotherapy (etoposide and carboplatin), followed by 2 high-dose thiotepa courses (600 mg/m2) with hematological stem cell support. At the latest 45 days after the last stem cell rescue, patients received risk-adapted craniospinal radiation therapy. Maintenance treatment with temozolomide was planned to start between 1–3 months after the end of radiotherapy. The primary endpoint was PFS. Outcome and safety analyses were per protocol (all patients who received at least one dose of induction chemotherapy).ResultsFifty-one patients (median age, 8 y; range, 5–19) were enrolled. The median follow-up was 7.1 years (range: 3.4–9.0). The 3 and 5-year PFS with their 95% confidence intervals (95% CI) were 78% (65–88) and 76% (63–86), and the 3 and 5-year OS were 84% (72–92) and 76% (63–86), respectively. Medulloblastoma subtype was a statistically significant prognostic factor (P-value = 0.039) with large-cell/anaplastic being of worse prognosis, as well as a molecular subgroup (P-value = 0.012) with sonic hedgehog (SHH) and group 3 being of worse prognosis than wingless (WNT) and group 4. Therapy was well tolerated.ConclusionsThis treatment based on high-dose chemotherapy and conventional radiotherapy resulted in a high survival rate in children with newly diagnosed high-risk medulloblastoma. 相似文献
25.
Muna Marashdeh Cameron Stewart Anil Kishen Celine Levesque Yoav Finer 《Journal of endodontics》2021,47(5):793-799
IntroductionThe purpose of this study was to assess the antimicrobial activity and flow of root canal sealers after incorporating novel highly loaded antimicrobial drug-silica coassembled particles (DSPs).MethodsDSPs were synthesized through coassembly of silica and octenidine dihydrochloride (OCT) antimicrobial surfactant. DSPs were loaded (1% and 2% wt) into epoxy resin sealer (AH Plus [AH]; Dentsply DeTrey GmbH, Konstanz, Germany) or calcium silicate–based sealer (EndoSequence Bioceramic Sealer (BC); Brasseler, Savannah, GA). OCT release from DSP-modified sealers was determined using liquid chromatography. Antimicrobial activity of sealers against planktonic or biofilm form Enterococcus faecalis was assessed using direct contact and membrane restricted tests. Sealer flow was tested according to ISO6876:2012.ResultsOCT release from BC + 1% or 2% DSPs was above the minimum inhibitory concentration following 2 days throughout the 30-day experiment, whereas OCT release from AH + 1% or 2% DSP was significantly below the minimum inhibitory concentration against E. faecalis (4 μg/mL) over the whole 30-day experimental period. All materials (with or without DSPs) killed planktonic bacteria initially. AH ± 1% or 2% DSPs had no antimicrobial activity after 7 days. BC + 1% or 2% DSPs maintained antibacterial activity over the 30-day period. Both modified and unmodified sealers completely inhibited the growth of E. faecalis biofilms after 24 hours of contact. DSPs decreased the flow of AH and BC sealers; for AH, the reduction was proportional to the amount of DSPs added. All modified and unmodified sealers, except for AH + 2% DSPs, were within the acceptable limits of ISO 6876 flow tests.ConclusionsDSPs enhanced the antimicrobial performance of BC but not AH, whereas the material’s flow remained compliant with ISO 6876 standards. Depending on the sealer, DSPs may enhance antimicrobial efficacy in root canal treatment and potentially improve treatment outcome. 相似文献
26.
Zuzana Deans Melissa Hill Lyn S Chitty Celine Lewis 《European journal of human genetics : EJHG》2013,21(7):713-718
Non-invasive prenatal testing for single gene disorders is now clearly on the horizon. This new technology offers obvious clinical benefits such as safe testing early in pregnancy. Before widespread implementation, it is important to consider the possible ethical implications. Four hypothetical scenarios are presented that highlight how ethical ideals of respect for autonomy, privacy and fairness may come into play when offering non-invasive prenatal testing for single gene disorders. The first scenario illustrates the moral case for using these tests for ‘information only'', identifying a potential conflict between larger numbers of women seeking the benefits of the test and the wider social impact of funding tests that do not offer immediate clinical benefit. The second scenario shows how the simplicity and safety of non-invasive prenatal testing could lead to more autonomous decision-making and, conversely, how this could also lead to increased pressure on women to take up testing. In the third scenario we show how, unless strong safeguards are put in place, offering non-invasive prenatal testing could be subject to routinisation with informed consent undermined and that woman who are newly diagnosed as carriers may be particularly vulnerable. The final scenario introduces the possibility of a conflict of the moral rights of a woman and her partner through testing for single gene disorders. This analysis informs our understanding of the potential impacts of non-invasive prenatal testing for single gene disorders on clinical practice and has implications for future policy and guidelines for prenatal care. 相似文献
27.
Patrice Chevallier Nelly Robillard Marina Illiaquer Julie Esbelin Mohamad Mohty Celine Bodin-Bressollette Thierry Guillaume Veronique Stocco Fabienne Auffray Sophie Derenne Lucie Planche Marie-Christine Bene Berthe-Marie Imbert-Marcille 《Journal of clinical virology》2013,56(4):331-335
BackgroundCord Blood (CB) are increasingly used as an alternative stem cells source in adults for allogeneic Stem Cell Transplantation (allo-SCT). The risk of human herpesvirus (HHV-6) reactivation is significantly higher after CB transplant vs unrelated peripheral blood stem cells (PBSC) allo-SCT. Higher HHV-6 cell receptor CD46 expression on progenitor cells in CB may explain this difference.ObjectivesTo prospectively compare the HHV-6 cell receptor CD46 expression on various cell subsets of three freshly harvested blood sources on one hand and of three graft sources on the other hand.Study design52 samples were used for the purpose of this study. They were issued from peripheral blood (PB, n = 10), G-CSF mobilised PB (GCSF-PB, n = 10), cord blood (CB, n = 10), unmanipulated bone marrow (uBM, n = 5), leukapheresis product (LP, n = 10) and thawed CB graft (n = 7). CD46 expression was assessed by FACS analysis on total lymphocytes, monocytes, NK cells, T and B cells subsets, plasmacytoid (pDCs) dendritic cells and stem cells.ResultsAs all cell subsets were found CD46 positive, CD46 mean fluorescence intensity (MFI) was then considered for comparison between the three blood sources and the three graft sources. The most impressive result observed was that HHV-6 cell receptor CD46 expression was significantly reduced in almost all cell components of thawed CB graft compared to other graft sources.ConclusionsThis original study shows strong differences in term of quantitative CD46 expression between several blood and grafts samples. Our results suggest that other factors than the qualitative CD46 expression play a role in the higher HHV-6 reactivation observed after CB transplant in adults. 相似文献
28.
Lutfiye Oksuz Celine Dupieux Anne Tristan Michele Bes Jerome Etienne Nezahat Gurler 《International journal of medical sciences》2013,10(12):1740-1745
Background: To characterize the methicillin-resistant Staphylococcus aureus (MRSA) clones present in Istanbul, 102 MRSA isolates collected during a 5-year period at the Istanbul Medical Faculty Hospital were characterized using microarray analysis and phenotypic resistance profiles.Methods: Resistance to methicillin was detected with a cefoxitin disk diffusion assay and confirmed with a MRSA-agar and MRSA detection kit. Antimicrobial susceptibility testing was performed by a disk diffusion assay and interpreted according to the 2012 guidelines of the Antibiogram Committee of the French Society for Microbiology. Decreased susceptibility to glycopeptides was confirmed using the population analysis profile-area under the curve (PAP-AUC) method. The presence of the mecA gene was detected by polymerase chain reaction. Bacterial DNA was extracted according to the manufacturer''s recommended protocol using commercial extraction kits. Strains were extensively characterized using the DNA microarray.Results: Isolates were grouped into six clonal complexes. The most frequently detected clone was the Vienna/Hungarian/Brazilian clone (ST239-MRSA-III), which accounted for 53.9% of the isolates. These isolates were resistant to multiple antibiotics, particularly penicillin, tetracycline, rifampicin, kanamycin, tobramycin, gentamicin, levofloxacin, erythromycin, lincomycin and fosfomycin. Furthermore, three isolates were detected by population analysis profile as heterogeneous vancomycin-intermediate S. aureus (hVISA). The UK-EMRSA-15 clone (ST22-MRSA-IV PVL negative) was detected in 9.8% of the isolates and was mainly susceptible to all anti-staphylococcal antibiotics. Seven isolates (6.9%) were positive for PVL genes and were assigned to the CC80-MRSA-IV clone (European CA-MRSA clone, three isolates), ST8-MRSA-IV clone (USA300 clone, two isolates, one ACME-positive) or ST22-MRSA-IV clone (“Regensburg EMRSA” clone, two isolates). All other clones were detected in one to six isolates and corresponded to well-known clones (e.g., Pediatric clone, Dublin EMRSA clone, WA MRSA-54/63, WA MRSA-1/57).Conclusions: This work highlighted both the high prevalence of ST239-MRSA-III clone and the large diversity of the other MRSA clones detected in a university hospital in Istanbul. 相似文献
29.
Théo Maulet Samuel Pouplin Djamel Bensmail Raphael Zory Nicolas Roche Celine Bonnyaud 《Annals of physical and rehabilitation medicine》2021,64(4):101450
BackgroundBotulinum toxin injection (BTI) reduces muscle hyperactivity, but its effect on active upper-limb function is limited. Intensive rehabilitation could optimize the effects; however, outpatient post-stroke rehabilitation is usually not intensive. One solution could be self-rehabilitation.ObjectivesThe aim of this randomized controlled trial was to determine the effect of a self-rehabilitation program combined with BTI on upper-limb function in individuals with chronic hemiparesis.MethodsIn total, 33 outpatients were randomly allocated to receive BTI + self-rehabilitation (R group: n = 17) or BTI alone (C group: n = 16). Outcomes evaluated just before the BTI and 4 weeks later included the Wolf Motor Function Test (WMFT time: primary outcome), Action Research Arm Test, fatigue and quality of life.ResultsChange in WMFT did not differ between groups at 4 weeks (WMFT time: ?14% for R group, ?4% for C group. WFMT score: +12% for R group, 0% in C group). WFMT time and score improved significantly in the R group only (?14%, P = 0.01, and +12%, P = 0.02). In addition, the proportion of patients with improved WMFT time and score was higher in the R than C group (R group: 71% improved score, 77% improved time; C group: 43% improved score, 50% improved time). Also, passive range of shoulder flexion (P = 0.03) and wrist extension (P = 0.01) improved only in the R group. No other variables changed significantly. Compliance was excellent; average daily training time was greater than that prescribed.ConclusionsThe addition of a self-rehabilitation program to BTI did not significantly improve functional outcomes more than BTI alone; however, movement quality and speed improved only in the self-rehabilitation group. Participants in the self-rehabilitation group trained more than they were asked to, which suggests that they found the program worthwhile. These clinically relevant findings justify larger-scale studies of the effects of self-rehabilitation to enhance the effects of BTI. Clinical trial: NCT02699762. 相似文献
30.