全文获取类型
收费全文 | 936篇 |
免费 | 62篇 |
国内免费 | 2篇 |
专业分类
耳鼻咽喉 | 25篇 |
儿科学 | 15篇 |
妇产科学 | 28篇 |
基础医学 | 124篇 |
口腔科学 | 50篇 |
临床医学 | 140篇 |
内科学 | 161篇 |
皮肤病学 | 28篇 |
神经病学 | 51篇 |
特种医学 | 11篇 |
外科学 | 118篇 |
综合类 | 10篇 |
预防医学 | 88篇 |
眼科学 | 7篇 |
药学 | 45篇 |
中国医学 | 1篇 |
肿瘤学 | 98篇 |
出版年
2023年 | 10篇 |
2022年 | 12篇 |
2021年 | 24篇 |
2020年 | 16篇 |
2019年 | 22篇 |
2018年 | 33篇 |
2017年 | 17篇 |
2016年 | 22篇 |
2015年 | 28篇 |
2014年 | 33篇 |
2013年 | 52篇 |
2012年 | 78篇 |
2011年 | 74篇 |
2010年 | 42篇 |
2009年 | 44篇 |
2008年 | 59篇 |
2007年 | 68篇 |
2006年 | 37篇 |
2005年 | 51篇 |
2004年 | 45篇 |
2003年 | 48篇 |
2002年 | 48篇 |
2001年 | 8篇 |
2000年 | 13篇 |
1999年 | 12篇 |
1998年 | 9篇 |
1997年 | 9篇 |
1996年 | 5篇 |
1995年 | 3篇 |
1994年 | 9篇 |
1993年 | 4篇 |
1992年 | 5篇 |
1991年 | 9篇 |
1990年 | 9篇 |
1989年 | 5篇 |
1987年 | 2篇 |
1986年 | 5篇 |
1985年 | 1篇 |
1984年 | 4篇 |
1983年 | 2篇 |
1982年 | 1篇 |
1981年 | 3篇 |
1980年 | 5篇 |
1979年 | 6篇 |
1978年 | 1篇 |
1975年 | 1篇 |
1974年 | 2篇 |
1973年 | 1篇 |
1972年 | 1篇 |
1969年 | 1篇 |
排序方式: 共有1000条查询结果,搜索用时 953 毫秒
81.
Richard H. Epstein Joni M. Maga Michael E. Mahla Eric S. Schwenk Marc J. Bloom 《Journal canadien d'anesthésie》2018,65(5):512-521
Background
Processed electroencephalogram (EEG) monitors help assess the hypnotic state during general anesthesia or sedation. Maintaining the bispectral index (BIS) or state entropy (SE) between 40 and 60 has been recommended to mitigate anesthesia awareness. Nonetheless, SEs > 70 were frequently observed at end-tidal sevoflurane concentrations unlikely to allow awareness. We sought to determine the prevalence of elevated discordant measurements during BIS and SE monitoring.Methods
Electronic data collected over 11 months at two academic hospitals were retrospectively reviewed. At the hospital using SE, all cases were included with patients ≥ 18 yr and sevoflurane administered for at least 30 min during surgery. A cohort of cases propensity matched by age and American Society of Anesthesiologist Physical Status were selected from the hospital using BIS. Elevated discordant EEG indices were defined as values > 70 occurring during stable end-tidal sevoflurane concentrations > 1.5%. The odds ratio (OR) based on the probability of a case having at least one elevated discordant SE or BIS lasting ≥ two minutes (primary endpoint) was calculated.Results
At each hospital, 3,690 cases were studied. The mean (95% confidence interval [CI]) incidence of cases with at least one interval of an elevated discordant EEG index lasting at least two minutes was 3.6% (2.8% to 4.4%) for SE compared with 0.24% (0.17% to 0.27%) for BIS (pooled OR, 17.0; 95% CI, 8.3 to 34.7; P < 0.001).Conclusions
The prevalence of an elevated discordant EEG index is much greater with SE than with BIS. Elevated index values occurring at anesthetic concentrations well above the awareness threshold need to be assessed to determine if they indicate an inadequate depth of anesthesia requiring treatment or if they simply reflect the underlying monitoring algorithm.82.
83.
Zhong Y Carmella SG Upadhyaya P Hochalter JB Rauch D Oliver A Jensen J Hatsukami D Wang J Zimmerman C Hecht SS 《Chemical research in toxicology》2011,24(2):246-252
Polycyclic aromatic hydrocarbons (PAH) are among the likely major causative agents for lung cancer in smokers. PAH require metabolic activation to exert their carcinogenic effects, and one important pathway proceeds through a three-step sequence resulting in the formation of diol epoxides, which react with DNA to produce adducts that can cause mutations and initiate the carcinogenic process. However, no previous published studies have examined this critical pathway in humans specifically exposed to PAH by inhalation of cigarette smoke. This study used a unique approach employing a stable isotope derivative of phenanthrene, the simplest PAH with a bay region, a feature closely associated with PAH carcinogenicity. Twelve subjects each smoked a cigarette to which [D(10)]phenanthrene had been added. Plasma was analyzed for [D(10)]r-1,t-2,3,c-4-tetrahydroxy-1,2,3,4-tetrahydrophenanthrene ([D(10)]PheT), the major end product of the diol epoxide metabolism pathway of phenanthrene. The analysis was performed by gas chromatography--negative ion chemical ionization--tandem mass spectrometry, using [(13)C(6)]PheT as internal standard. The results demonstrated that the three-step pathway resulting in the formation of diol epoxides, as monitored by [D(10)]PheT, occurred with remarkable rapidity. Levels of [D(10)]PheT in plasma of all subjects were maximal at the earliest time points examined, 15-30 min after smoking the cigarette containing [D(10)]phenanthrene, and decreased thereafter. These results demonstrate that the formation of a PAH diol epoxide occurs rapidly in smokers. Because PAH diol epoxides are mutagenic and carcinogenic, the results clearly demonstrate immediate negative health consequences of smoking, which should serve as a major warning to anyone contemplating initiating tobacco use. 相似文献
84.
Researchers have recently demonstrated the presence of anti-HIV-1 microRNAs (miR-28, miR-125b, miR-150, miR-223, and miR-382) in monocytes, macrophages, and CD4+ T cells, which are the primary targets of HIV infection. These miRNAs appear to regulate the level of infectivity of HIV-1 in the target cells, and thus have an impact on HIV-1 latency. The levels of these miRNAs are significantly higher in resting CD4+ T cells than those in active CD4+ T cells, whereas HIV-1 infectivity is greater in active than in resting CD4+ T cells. Similarly, the levels of these miRNAs are significantly higher in monocytes than in macrophages, whereas HIV-1 infectivity is greater in macrophages than in monocytes. Down-regulation or inhibition of the activity of these miRNAs can promote replication of latent HIV-1 in resting CD4+ T cells and in monocytes. Recently, morphine was shown to down regulate the expression of anti-HIV miRNAs (miRNA-28, 125b, 150, and 382) in cultured human monocytes and this effect of morphine was mediated via activation of mu opioid receptors (MOR). In addition, levels of these anti-HIV miRNAs were significantly lower in the peripheral blood mononuclear cells (PBMCs) isolated from heroin-dependent subjects than those from control subjects. These findings raise an important question: Does morphine have potential to activate latent HIV-1 in resting CD4+ T cells and macrophages, including microglia of human subjects maintained on highly active antiretroviral therapy (HAART)? Further research is required to answer this question. 相似文献
85.
Van LP Bardel E Gregoire S Vanoirbeek J Schneider E Dy M Thieblemont N 《European journal of immunology》2011,41(7):1992-1999
The evolution of allergic asthma is tightly controlled by effector and regulatory cells, as well as cytokines such as IL-10 and/or TGF-β, and it is widely acknowledged that environmental exposure to allergens and infectious agents can influence these processes. In this context, the recognition of pathogen-associated motifs, which trigger TLR activation pathways, plays a critical role with important consequences for disease progression and outcome. We addressed the question whether the TLR7 ligand resiquimod (R848), which has been shown to be protective in several experimental allergic asthma protocols, can also suppress typical asthma symptoms once the disease is established. To this end, we used an OVA-induced experimental model of murine allergic asthma in which R848 was injected after a series of challenges with aerosolized OVA. We found that the treatment attenuated allergic symptoms through a mechanism that required Tregs, as assessed by the expansion of this population in the lungs of mice having received R848, and the loss of R848-mediated suppression of allergic responses after in vivo Treg depletion. IL-10 provided only a minor contribution to this suppressive effect that was largely mediated through a TGF-β-dependent pathway, a finding that opens new therapeutic opportunities for the pharmacological targeting of Tregs. 相似文献
86.
Chimowitz MI Lynn MJ Derdeyn CP Turan TN Fiorella D Lane BF Janis LS Lutsep HL Barnwell SL Waters MF Hoh BL Hourihane JM Levy EI Alexandrov AV Harrigan MR Chiu D Klucznik RP Clark JM McDougall CG Johnson MD Pride GL Torbey MT Zaidat OO Rumboldt Z Cloft HJ;SAMMPRIS Trial Investigators 《The New England journal of medicine》2011,365(11):993-1003
87.
Pritt BS Sloan LM Johnson DK Munderloh UG Paskewitz SM McElroy KM McFadden JD Binnicker MJ Neitzel DF Liu G Nicholson WL Nelson CM Franson JJ Martin SA Cunningham SA Steward CR Bogumill K Bjorgaard ME Davis JP McQuiston JH Warshauer DM Wilhelm MP Patel R Trivedi VA Eremeeva ME 《The New England journal of medicine》2011,365(5):422-429
88.
Turunen JA Peltonen JO Pietiläinen OP Hennah W Loukola A Paunio T Silander K Ekelund J Varilo T Partonen T Lönnqvist J Peltonen L 《Schizophrenia Research》2007,91(1-3):27-36
Several putative schizophrenia susceptibility genes have recently been identified. Significant associations between schizophrenia and neuregulin 1 (NRG1) and dysbindin (DTNBP1) were first reported in 2002 and studies in several populations have since independently reported positive associations to these gene regions. Further, both tentative functional and genetic data have implicated the role of AKT1 in the genetic background of this disorder. However, findings have not been consistent in all populations. We investigated the allelic diversity of these three genes NRG1, DTNBP1 and AKT1 in a representative nation-wide study sample of 441 Finnish schizophrenia families consisting of 865 affected individuals, in order to assess their role in one of the largest population-based study samples. DTNBP1 and AKT1 failed to show evidence of association, whereas two SNPs in the 3' region of the NRG1 gene yielded suggestive evidence of association (p=0.012 and p=0.048) in family-based association analyses. Thus, our study does not indicate that AKT1 or DTNBP1 play a role in the etiology of schizophrenia in the Finnish population. Furthermore, results do not support a major role for NRG1, but we cannot completely exclude a minor role of this gene in the Finnish population. 相似文献
89.
Elvire Bourgeois Linh Pham Van Michel Samson Sverine Diem Anne Barra Stphane Roga Jean‐Marc Gombert Elke Schneider Michel Dy Pierre Gourdy Jean‐Philippe Girard Andr Herbelin 《European journal of immunology》2009,39(4):1046-1055
IL‐33 has recently been identified as a cytokine endowed with pro‐Th2 functions, raising the question of its effect on invariant natural killer T cell (iNKT), which are potent IL‐4 producers. Here, we report a two‐fold increase of iNKT‐cell counts in spleen and liver after a 7‐day treatment of mice with IL‐33, which results from a direct effect, given that purified iNKT cells express the T1/ST2 receptor constitutively and respond to IL‐33 by in vitro expansion and functional activation. Conversely to the expected pro‐Th2 effect, IL‐33 induced a preferential increase in IFN‐γ rather than IL‐4 production upon TCR engagement that depended on endogenous IL‐12. Moreover, in combination with the pro‐inflammatory cytokine IL‐12, IL‐33 enhanced IFN‐γ production by both iNKT and NK cells. Taken together these data support the conclusion that IL‐33 can contribute as a co‐stimulatory factor to innate cellular immune responses. 相似文献