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Derek K. Chu Romina Brignardello-Petersen Gordon H. Guyatt Cristian Ricci Jon Genuneit 《Pediatric allergy and immunology》2022,33(1):e13609
Network meta-analyses (NMAs) simultaneously estimate the effects of multiple possible treatment options for a given clinical presentation. For allergists to benefit optimally from NMAs, they must understand the process and be able to interpret the results. Through a worked example published in Pediatric Allergy and Immunology, we summarize how to identify credible NMAs and interpret them with a focus on recent innovations in the GRADE approach (Grading of Recommendations Assessment, Development, and Evaluation). NMAs build on traditional systematic reviews and meta-analyses that consider only direct paired comparisons by including indirect evidence, thus allowing the simultaneous assessment of the relative effect of all pairs of competing alternatives. Our framework informs clinicians of how to identify credible NMAs and address the certainty of the evidence. Trustworthy NMAs fill a critical gap in providing key inferences using direct and indirect evidence to inform clinical decision making when faced with more than two competing courses of treatment options. This document will help allergists to identify trustworthy NMAs to enhance patient care. 相似文献
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Hanchen Xu Kevin Van der Jeught Zhuolong Zhou Lu Zhang Tao Yu Yifan Sun Yujing Li Changlin Wan Ka Man So Degang Liu Michael Frieden Yuanzhang Fang Amber L. Mosley Xiaoming He Xinna Zhang George E. Sandusky Yunlong Liu Samy O. Meroueh Chi Zhang Aruna B. Wijeratne Cheng Huang Guang Ji Xiongbin Lu 《The Journal of clinical investigation》2021,131(10)
One of the primary mechanisms of tumor cell immune evasion is the loss of antigenicity, which arises due to lack of immunogenic tumor antigens as well as dysregulation of the antigen processing machinery. In a screen for small-molecule compounds from herbal medicine that potentiate T cell–mediated cytotoxicity, we identified atractylenolide I (ATT-I), which substantially promotes tumor antigen presentation of both human and mouse colorectal cancer (CRC) cells and thereby enhances the cytotoxic response of CD8+ T cells. Cellular thermal shift assay (CETSA) with multiplexed quantitative mass spectrometry identified the proteasome 26S subunit non–ATPase 4 (PSMD4), an essential component of the immunoproteasome complex, as a primary target protein of ATT-I. Binding of ATT-I with PSMD4 augments the antigen-processing activity of immunoproteasome, leading to enhanced MHC-I–mediated antigen presentation on cancer cells. In syngeneic mouse CRC models and human patient–derived CRC organoid models, ATT-I treatment promotes the cytotoxicity of CD8+ T cells and thus profoundly enhances the efficacy of immune checkpoint blockade therapy. Collectively, we show here that targeting the function of immunoproteasome with ATT-I promotes tumor antigen presentation and empowers T cell cytotoxicity, thus elevating the tumor response to immunotherapy. 相似文献
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Kenta Matsuda Stephen A. Migueles Jinghe Huang Lyuba Bolkhovitinov Sarah Stuccio Trevor Griesman Alyssa A. Pullano Byong H Kang Elise Ishida Matthew Zimmerman Neena Kashyap Kelly M. Martins Daniel Stadlbauer Jessica Pederson Andy Patamawenu Nathaniel Wright Tulley Shofner Sean Evans C. Jason Liang Julin Candia Angelique Biancotto Giovanna Fantoni April Poole Jon Smith Jeff Alexander Marc Gurwith Florian Krammer Mark Connors 《The Journal of clinical investigation》2021,131(5)
BACKGROUNDTo understand the features of a replicating vaccine that might drive potent and durable immune responses to transgene-encoded antigens, we tested a replication-competent adenovirus type 4 encoding influenza virus H5 HA (Ad4-H5-Vtn) administered as an oral capsule or via tonsillar swab or nasal spray.METHODSViral shedding from the nose, mouth, and rectum was measured by PCR and culturing. H5-specific IgG and IgA antibodies were measured by bead array binding assays. Serum antibodies were measured by a pseudovirus entry inhibition, microneutralization, and HA inhibition assays.RESULTSAd4-H5-Vtn DNA was shed from most upper respiratory tract–immunized (URT-immunized) volunteers for 2 to 4 weeks, but cultured from only 60% of participants, with a median duration of 1 day. Ad4-H5-Vtn vaccination induced increases in H5-specific CD4+ and CD8+ T cells in the peripheral blood as well as increases in IgG and IgA in nasal, cervical, and rectal secretions. URT immunizations induced high levels of serum neutralizing antibodies (NAbs) against H5 that remained stable out to week 26. The duration of viral shedding correlated with the magnitude of the NAb response at week 26. Adverse events (AEs) were mild, and peak NAb titers were associated with overall AE frequency and duration. Serum NAb titers could be boosted to very high levels 2 to 5 years after Ad4-H5-Vtn vaccination with recombinant H5 or inactivated split H5N1 vaccine.CONCLUSIONReplicating Ad4 delivered to the URT caused prolonged exposure to antigen, drove durable systemic and mucosal immunity, and proved to be a promising platform for the induction of immunity against viral surface glycoprotein targets.TRIAL REGISTRATIONClinicalTrials.gov and NCT01443936.FUNDINGIntramural and Extramural Research Programs of the NIAID, NIH (U19 AI109946) and the Centers of Excellence for Influenza Research and Surveillance (CEIRS), NIAID, NIH (contract HHSN272201400008C). NCT01806909相似文献
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Nancy Khardori 《Indian journal of medical microbiology》2022,40(2):187-192
BackgroundEdward Jenner, by any definition would be considered the father of vaccinology. His use of cow pox virus for vaccinating against small pox is the prime example of a live vaccine. Using a virus that has very low virulence for humans and therefore, fits the definition of attenuated. Hesitancy towards a vaccine of this type, much before the science of microbiology and immunology were established, would have been justifiable. In the first half of 20th century, large number of vaccines became available for childhood diseases with significant morbidity and mortality. Around the same time global travel and trade led to escalation in the widespread transmission of diseases caused by microbes.ObjectiveThe objective of this narrative is to offer a balanced view of science behind vaccines, their current status and advances expected in the near future. At the same time the various types of reactions from public at large towards vaccines over past decades are reviewed.ContentThis narrative provides a historical perspective of vaccine development, reviews mechanisms of vaccine induced protection, currently available vaccine technologies and vaccines. The focus is on newer vaccines including those utilizing viral vectors and gene based vaccines. Based on the times during which this narrative is being written, messenger RNA vaccines are discussed in detail.ConclusionThe content and review of literature offered in this review makes the impact of vaccines on human life clear. It is also to be accepted that resistance and hesitation towards vaccines is nothing new or limited to vaccines being used during the ongoing pandemic of Covid 19. The continued development of science and products of vaccinology is necessary for further impact on human life. The development of a strong public health infrastructure by nations around the world is the key to improve upon current efforts at public awareness, proactive interventions and appropriate vaccine utilization during all times. Preparedness for epidemics and pandemics would then become more and more efficient than currently in existence. 相似文献
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《La Revue de médecine interne / fondée ... par la Société nationale francaise de médecine interne》2022,43(2):89-97
Anticytoplasmic neutrophil antibodies (ANCA)-associated vasculitis (AAV) are rare systemic immune-mediated diseases characterized by small vessel necrotizing vasculitis and/or respiratory tract inflammation. Over the last 2 decades, anti-MPO vasculitis mouse model has enlightened the role of ANCA, neutrophils, complement activation, T helper cells (Th1, Th17) and microbial agents. In humans, CD4T cells have been extensively studied, while the dramatic efficacy of rituximab demonstrated the key role of B cells. Many areas of uncertainty remain, such as the driving force of GPA extra-vascular granulomatous inflammation and the relapse risk of anti-PR3 AAV pathogenesis. Animal models eventually led to identify complement activation as a promising therapeutic target. New investigation tools, which permit in depth immune profiling of human blood and tissues, may open a new era for the studying of AAV pathogenesis. 相似文献
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Yu-chuan Liu Wen-ya Lin Ming-chin Tsai Lin-shien Fu 《Journal of microbiology, immunology, and infection》2019,52(3):480-486
BackgroundTo investigate the association of systemic lupus erythematosus (SLE) with thyroid diseases in a medical center in central Taiwan.MethodsThis is a retrospective cohort of 2796 SLE patients in a tertiary referral medical center from 2000 to 2013. We screened SLE by catastrophic illness registration from national insurance bureau; and thyroid diseases by ICD 9 codes, then confirmed by thyroid function test, auto-antibody, medical and/or surgical intervention. We compared the rate of hyperthyroidism, hypothyroidism and autoimmune thyroid disease (AITD) in SLE patients and the 11,184 match controls. We calculated the rate of these thyroid diseases and positive antibodies to thyroglobulin (ATGAb), thyroid peroxidase (TPOAb) in SLE patients grouped by the presence of overlap syndrome and anti-dsDNA antibody. We also compared the association of thyroid diseases to severe SLE conditions, including renal, central nervous system (CNS) involvement, and thrombocytopenia.ResultsCompared to the matched controls, the cumulative incidence of thyroid disease, including hyperthyroidism, hypothyroidism and AITD, were all higher in SLE patients (p < 0.0001). The average age of SLE patients with thyroid diseases patients were older than those without thyroid diseases (p = 0.002). Those had euthyroid AITD were younger than other patients with thyroid diseases (p = 0.02). Up to 30.3% SLE patients had overlap syndrome and had higher relative risk of thyroid diseases than those without overlap syndrome, in terms of hypothyroidism and AITD, but not hyperthyroidism. SLE patients with thyroid diseases also carry higher risk for severe complications such as renal involvement (p = 0.024) central nervous system involvement (p < 0.0001).ConclusionSLE patients had significantly higher rate of hyperthyroidism, hypothyroidism, and AITD than the matched control. Among lupus patients, the risks of thyroid diseases are even higher in the presence of overlap syndrome. SLE patients with thyroid diseases had higher risk of renal and CNS involvement. 相似文献
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Rie Sakai-Bizmark Scott M.I. Friedlander Karin Oshima Eliza J. Webber Laurie A. Mena Emily H. Marr Yoshikazu Ohtsuka 《Allergology international》2019,68(3):316-320
BackgroundAnaphylaxis is a severe and potentially fatal allergic response. Early-life exposure to rural environments may help protect against allergic reaction. This study assesses urban/rural differences by age and race/ethnicity in emergency department (ED) pediatric visit rates for food-induced anaphylaxis.MethodsThis observational study examined 2009–2014 inpatient and ED data from New York and Florida, using ICD-9-CM diagnostic code (995.6) to identify food-induced anaphylaxis cases <18 y/o. Primary predictor of interest was urban/rural setting, with race/ethnicity and age also evaluated. Associations between ED visit rates and urban/rural setting were evaluated by multivariable hierarchical negative binomial regression with state and year fixed effects.ResultsED visit rates (per 100,000) for food-induced anaphylaxis were 12.31 and 4.60 in urban and rural settings, respectively. Rates were highest among Blacks (15.26) younger urban children (17.29) and older rural children (6.99). Compared to rural, urban children had significantly higher anaphalaxis ED visit rates (IRR 2.77).ConclusionsFood-induced anaphylaxis ED visit rates were highest among younger urban children and Black children, with a notable contrast in age distribution between urban and rural rates. Higher urban rates may be attributed to Hygiene Hypothesis, though racial, economic and emergency care access disparities may also influence these outcomes. 相似文献