全文获取类型
收费全文 | 35593篇 |
免费 | 6859篇 |
国内免费 | 106篇 |
学科分类
医药卫生 | 42558篇 |
出版年
2024年 | 199篇 |
2023年 | 1311篇 |
2022年 | 857篇 |
2021年 | 1603篇 |
2020年 | 1769篇 |
2019年 | 1159篇 |
2018年 | 1913篇 |
2017年 | 1785篇 |
2016年 | 2099篇 |
2015年 | 2074篇 |
2014年 | 2801篇 |
2013年 | 3225篇 |
2012年 | 2280篇 |
2011年 | 2228篇 |
2010年 | 1914篇 |
2009年 | 2227篇 |
2008年 | 1708篇 |
2007年 | 1515篇 |
2006年 | 1647篇 |
2005年 | 1242篇 |
2004年 | 1097篇 |
2003年 | 932篇 |
2002年 | 807篇 |
2001年 | 370篇 |
2000年 | 311篇 |
1999年 | 343篇 |
1998年 | 446篇 |
1997年 | 355篇 |
1996年 | 308篇 |
1995年 | 271篇 |
1994年 | 214篇 |
1993年 | 157篇 |
1992年 | 155篇 |
1991年 | 139篇 |
1990年 | 151篇 |
1989年 | 107篇 |
1988年 | 89篇 |
1987年 | 75篇 |
1986年 | 76篇 |
1985年 | 76篇 |
1984年 | 71篇 |
1983年 | 65篇 |
1982年 | 35篇 |
1981年 | 38篇 |
1980年 | 37篇 |
1979年 | 21篇 |
1978年 | 36篇 |
1977年 | 29篇 |
1976年 | 22篇 |
1972年 | 20篇 |
排序方式: 共有10000条查询结果,搜索用时 0 毫秒
951.
952.
Paolo Paganetti Julia Reichwald Dorothee Bleckmann Dorothee Abramowski Domenico Ammaturo Carmen Barske Simone Danner Maurizio Molinari Matthias Müller Stéphanie Papin Sabine Rabe Peter Schmid Matthias Staufenbiel 《Neurobiology of aging》2013,34(12):2866-2878
Heterologous expression of the functional amyloid beta (Aβ) antibody β1 in the central nervous system was engineered to maximize antibody exposure in the brain and assess the effects on Aβ production and accumulation in these conditions. A single open reading frame encoding the heavy and light chains of β1 linked by the mouth and foot virus peptide 2A was expressed in brain neurons of transgenic mice. Two of the resulting BIN66 transgenic lines were crossed with APP23 mice, which develop severe central amyloidosis. Brain concentrations at steady-state 5 times greater than those found after peripheral β1 administration were obtained. Similar brain and plasma β1 concentrations indicated robust antibody efflux from the brain. In preplaque mice, β1 formed a complex with Aβ that caused a modest Aβ increase in brain and plasma. At 11 months of age, β1 expression reduced amyloid by 97% compared with age-matched APP23 mice. Interference of β1 with β-secretase cleavage of amyloid precursor protein was relatively small. Our data suggest that severely impaired amyloid formation was primarily mediated by a complex of β1 with soluble Aβ, which might have prevented Aβ aggregation or favored transport out of the brain. 相似文献
953.
954.
Ulrike Schliesser Martin Chopra Andreas Beilhack Christine Appelt Simone Vogel Julia Schumann Ivo Panov Katrin Vogt Stephan Schlickeiser Sven Olek Kathryn Wood Christine Brandt Hans‐Dieter Volk Birgit Sawitzki 《European journal of immunology》2013,43(12):3291-3305
The transfer of alloreactive regulatory T (aTreg) cells into transplant recipients represents an attractive treatment option to improve long‐term graft acceptance. We recently described a protocol for the generation of aTreg cells in mice using a nondepleting anti‐CD4 antibody (aCD4). Here, we investigated whether adding TGF‐β and retinoic acid (RA) or rapamycin (Rapa) can further improve aTreg‐cell generation and function. Murine CD4+ T cells were cultured with allogeneic B cells in the presence of aCD4 alone, aCD4+TGF‐β+RA or aCD4+Rapa. Addition of TGF‐β+RA or Rapa resulted in an increase of CD25+Foxp3+‐expressing T cells. Expression of CD40L and production of IFN‐γ and IL‐17 was abolished in aCD4+TGF‐β+RA aTreg cells. Additionally, aCD4+TGF‐β+RA aTreg cells showed the highest level of Helios and Neuropilin‐1 co‐expression. Although CD25+Foxp3+ cells from all culture conditions displayed complete demethylation of the Treg‐specific demethylated region, aCD4+TGF‐β+RA Treg cells showed the most stable Foxp3 expression upon restimulation. Consequently, aCD4+TGF‐β+RA aTreg cells suppressed effector T‐cell differentiation more effectively in comparison to aTreg cells harvested from all other cultures, and furthermore inhibited acute graft versus host disease and especially skin transplant rejection. Thus, addition of TGF‐β+RA seems to be superior over Rapa in stabilising the phenotype and functional capacity of aTreg cells. 相似文献
955.
Julia Schaake Malte Kronshage Frank Uliczka Manfred Rohde Tobias Knuuti Eckhard Strauch Angelika Fruth Melissa Wos-Oxley Petra Dersch 《Infection and immunity》2013,81(11):4013-4025
Yersinia enterocolitica is a human pathogen that is ubiquitous in livestock, especially pigs. The bacteria are able to colonize the intestinal tract of a variety of mammalian hosts, but the severity of induced gut-associated diseases (yersiniosis) differs significantly between hosts. To gain more information about the individual virulence determinants that contribute to colonization and induction of immune responses in different hosts, we analyzed and compared the interactions of different human- and animal-derived isolates of serotypes O:3, O:5,27, O:8, and O:9 with murine, porcine, and human intestinal cells and macrophages. The examined strains exhibited significant serotype-specific cell binding and entry characteristics, but adhesion and uptake into different host cells were not host specific and were independent of the source of the isolate. In contrast, survival and replication within macrophages and the induced proinflammatory response differed between murine, porcine, and human macrophages, suggesting a host-specific immune response. In fact, similar levels of the proinflammatory cytokine macrophage inflammatory protein 2 (MIP-2) were secreted by murine bone marrow-derived macrophages with all tested isolates, but the equivalent interleukin-8 (IL-8) response of porcine bone marrow-derived macrophages was strongly serotype specific and considerably lower in O:3 than in O:8 strains. In addition, all tested Y. enterocolitica strains caused a considerably higher level of secretion of the anti-inflammatory cytokine IL-10 by porcine than by murine macrophages. This could contribute to limiting the severity of the infection (in particular of serotype O:3 strains) in pigs, which are the primary reservoir of Y. enterocolitica strains pathogenic to humans. 相似文献
956.
Jay PortnoyGinger L. Chew ScD Wanda PhipatanakulP. Brock Williams PhD Carl GrimesKevin Kennedy MPH Elizabeth C. MatsuiJ. David Miller PhD David BernsteinJoann Blessing-Moore MD Linda CoxDavid Khan MD PhD David LangRichard Nicklas MD John OppenheimerChristopher Randolph MD Diane SchullerSheldon Spector MD Stephen A. TillesDana Wallace MD James SeltzerJames Sublett MD 《The Journal of allergy and clinical immunology》2013
957.
Julia Graham Gholamreza Salimi-Khorshidi Cindy Hagan Nicholas Walsh Ian Goodyer Belinda Lennox John Suckling 《Journal of affective disorders》2013
Background
Major Depressive Disorder (MDD) is a leading cause of disease burden worldwide. With the rapid growth of neuroimaging research on relatively small samples, meta-analytic techniques are becoming increasingly important. Here, we aim to clarify the support in fMRI literature for three leading neurobiological models of MDD: limbic–cortical, cortico–striatal and the default mode network.Methods
Searches of PubMed and Web of Knowledge, and manual searches, were undertaken in early 2011. Data from 34 case-control comparisons (n=1165) and 6 treatment studies (n=105) were analysed separately with two meta-analytic methods for imaging data: Activation Likelihood Estimation and Gaussian-Process Regression.Results
There was broad support for limbic–cortical and cortico–striatal models in the case-control data. Evidence for the role of the default mode network was weaker. Treatment-sensitive regions were primarily in lateral frontal areas.Limitations
In any meta-analysis, the increase in the statistical power of the inference comes with the risk of aggregating heterogeneous study pools. While we believe that this wide range of paradigms allows identification of key regions of dysfunction in MDD (regardless of task), we attempted to minimise such risks by employing GPR, which models such heterogeneity.Conclusions
The focus of treatment effects in frontal areas indicates that dysregulation here may represent a biomarker of treatment response. Since the dysregulation in many subcortical regions in the case-control comparisons appeared insensitive to treatment, we propose that these act as trait vulnerability markers, or perhaps treatment insensitivity. Our findings allow these models of MDD to be applied to fMRI literature with some confidence. 相似文献958.
Ivan J. Fuss Julia Friend Zhiqiong Yang Jian Ping He Lubna Hooda James Boyer Liqiang Xi Mark Raffeld David E. Kleiner Theo Heller Warren Strober 《Journal of clinical immunology》2013,33(4):748-758
Purpose
Patients with Common Variable Immunodeficiency (CVID) are subject to the development of a liver disease syndrome known as nodular regenerative hyperplasia (NRH). The purpose of this study was to define the characteristics and course of this complication of CVID.Methods
CVID patients were evaluated by retrospective and prospective clinical course review. Liver biopsy specimens were evaluated for evidence of NRH and studied via RT-PCR for cytokine analysis.Results
NRH in our CVID patient population occurred in approximately 5 % of the 261 patients in our total CVID study group, initially presenting in most cases with an elevated alkaline phosphatase level. While in some patients the disease remained static, in a larger proportion a more severe disease developed characterized by portal hypertension, the latter leading to hypersplenism with neutropenia and thrombocytopenia and, in some cases, to ascites. In addition, a substantial proportion of patients either developed or presented initially with an autoimmune hepatitis-like (AIH-like) liver disease that resulted in severe liver dysfunction and, in most cases to death due to infections. The liver histologic findings in these AIH-like patients were characterized by underlying NRH pattern with superimposed interface hepatitis, lymphocytic infiltration and fibrosis. Immunologic studies of biopsies of NRH patients demonstrated the presence of infiltrating T cells producing IFN-γ, suggesting that the NRH is due to an autoimmune process.Conclusion
Overall, these studies provide evidence that NRH may not be benign but, can be a severe and potentially fatal disease complication of CVID that merits close monitoring and intervention. 相似文献959.
Browne Julia Cather Corinne Zvonar Vanya Thayer Katherine Skiest Hannah Arntz Diana Kritikos Katherine Schnitzer Kristina Brown Hannah Evins A. Eden Donovan Abigail 《Community mental health journal》2021,57(5):864-871
Community Mental Health Journal - The mortality disparity for persons with schizophrenia spectrum disorders (SSDs) due to cardiovascular disease is a devastating problem. Many risk factors are... 相似文献
960.
Julia Große Moritz Bruno Petzold Ralf Brand Andreas Strhle 《International journal of methods in psychiatric research》2021,30(1):e1862
ObjectivesIncreasing the number of daily steps by using a pedometer and a diary leads to an activity increase and improved health outcomes in a variety of somatic disorders. Hence, for the inpatient treatment of depression, supervised exercise interventions are more widespread. We aim to examine if a self‐managed pedometer intervention (PI) with the option of being proceeded after discharge leads to reduction of depression and to a physical activity (PA) increase.MethodsThe Step Away from Depression (SAD) study is a multicenter randomized controlled trial targeting 400 patients with major depressive disorder. Treatment as usual (TAU) is compared to TAU plus PI after 4 weeks, at discharge, and 6 months after hospital admission. Primary outcomes are clinically rated depression severity and accelerometer‐measured step counts. Secondary outcomes include self‐reported depression symptoms and PA level, psychiatric symptoms, health‐related quality of life, self‐efficacy, and components of the Motivation Volition Process Model.ResultsWe report the design of the SAD study considering several methodological aspects for exercise studies, in general.ConclusionsResults of our study will provide information about efficacy of PI for inpatient treatment and about interrelating processes of change concerning depression, PA, and aspects of motivation and volition. 相似文献