首页 | 本学科首页   官方微博 | 高级检索  
文章检索
  按 检索   检索词:      
出版年份:   被引次数:   他引次数: 提示:输入*表示无穷大
  收费全文   652篇
  免费   59篇
  国内免费   3篇
耳鼻咽喉   10篇
儿科学   28篇
妇产科学   4篇
基础医学   137篇
口腔科学   1篇
临床医学   64篇
内科学   121篇
皮肤病学   6篇
神经病学   75篇
特种医学   24篇
外科学   53篇
综合类   9篇
预防医学   58篇
眼科学   10篇
药学   34篇
肿瘤学   80篇
  2023年   8篇
  2022年   17篇
  2021年   27篇
  2020年   17篇
  2019年   17篇
  2018年   24篇
  2017年   19篇
  2016年   22篇
  2015年   14篇
  2014年   29篇
  2013年   46篇
  2012年   61篇
  2011年   59篇
  2010年   39篇
  2009年   29篇
  2008年   30篇
  2007年   41篇
  2006年   33篇
  2005年   22篇
  2004年   19篇
  2003年   12篇
  2002年   8篇
  2001年   8篇
  2000年   3篇
  1999年   4篇
  1998年   3篇
  1997年   6篇
  1995年   4篇
  1993年   3篇
  1992年   4篇
  1990年   3篇
  1989年   5篇
  1988年   4篇
  1987年   5篇
  1986年   4篇
  1985年   3篇
  1984年   6篇
  1983年   3篇
  1982年   4篇
  1981年   5篇
  1980年   3篇
  1979年   2篇
  1978年   5篇
  1976年   2篇
  1975年   5篇
  1972年   5篇
  1971年   3篇
  1970年   2篇
  1966年   4篇
  1951年   2篇
排序方式: 共有714条查询结果,搜索用时 31 毫秒
1.
BACKGROUND: We evaluated historical trends in the Staphylococcus aureus infection rate, economic burden, and mortality in US hospitals from 1998 through 2003. METHODS: The Nationwide Inpatient Sample was used to assess trends over time of S. aureus infection during 1998-2003. Historical trends were determined for 5 strata of hospital stays, including all inpatient stays, surgical procedure stays, invasive cardiovascular surgical stays, invasive orthopedic surgical stays, and invasive neurosurgical stays. RESULTS: During the 6-year study period from 1998 through 2003, the rate of S. aureus infection increased significantly for all inpatient stays (from 0.74% to 1.0%; annual percentage change (APC), 7.1%; P=.004), surgical stays (from 0.90% to 1.3%; APC, 7.9%; P=.001), and invasive orthopedic surgical stays (from 1.2% to 1.8%; APC, 9.3%; P<.001). For invasive neurosurgical stays, the rate of S. aureus infection did not change from 1998 to 2000 but increased at an annual rate of 11.0% from 2000 to 2003 (from 1.4% to 1.8%; P=.034). The total economic burden of S. aureus infection for hospitals also increased significantly for all stay types, with the annual percentage increase ranging from 9.2% to 17.9% (P<.05 for all). In 2003, the total economic burden of S. aureus infection was estimated to be $14.5 billion for all inpatient stays and $12.3 billion for surgical patient stays. However, there were significant decreases in the risk of S. aureus-related in-hospital mortality from 1998 to 2003 for all inpatient stays (from 7.1% to 5.6%; APC, -4.6%; P=.001) and for surgical stays (from 7.1% to 5.5%; APC, -4.6%; P=.002). CONCLUSIONS: The inpatient S. aureus infection rate and economic burden of S. aureus infections for US hospitals increased substantially from 1998 to 2003, whereas the in-hospital mortality rate decreased.  相似文献   
2.
Specific immunological tolerance was induced in adult CBA mice by a single injection of deaggregated human IgG (dHGG). Spleen cells taken 7 to 42 days later, produced consistent suppression of a DNP-HGG collaborative antibody response on adoptive transfer into heavily irradiated recipients. Noncentrifuged F(ab')2 fragments of HGG were as effective as dHGG in the production of suppressor cells. Suppression was antigen-specific since HGG-tolerant cells failed to abrogate either a DNP-keyhole limpet hemocyanin collaborative response or antibody production to the noncross-reactive antigen, horse erythrocytes. Pretreatment of the tolerant cell population with anti-Thy-1 serum and complement reversed the suppressive effect. However, purified tolerant T cells obtained by passage through nylon wool or anti-Ig columns were less effective than the original spleen cells in mediating suppression. Analysis of the cell types appearing in the column effluents indicated that the reduction in suppressive activity is best explained by retention of T cells rather than macrophages. Different T cell populations, however, were retained on the two types of columns. In the case of anti-Ig columns, these consisted of Ly-2,3+, Ia+ effector cells, whereas nylon wool columns caused depletion of Ly-1,2,3+ cells which are known to act as amplifiers of suppression. Suppression could not be explained in terms of delay in differentiation of antibody-forming cell precursors since the effect persisted for up to 15 days after transfer of tolerant cells. The demonstration of a reduction in serum anti-DNP and anti-HGG antibodies excluded the possibility of antibody production in sites other than the spleen. A role for anti-carrier antibody-antigen complexes in mediating the effector phase of suppression was rendered unlikely by the finding that the suppressive effect of tolerant cells persisted in the absence of detectable anti-HGG antibody production. Effector T cells mediating suppression in this system were shown to bear the phenotype Ia+, Ly-2,3+ as judged by the effect of pretreatment with appropriate antisera and complement. They were spleen-seeking, but were not detected in the thymus or recirculating lymphocyte pool. Adult thymectomy failed to cause a significant reduction in suppressive activity by tolerant spleen cells indicating that at least a major component of the immediate precursors is not of recent thymic origin.  相似文献   
3.
Upon the discovery of numerous genes involved in the pathogenesis of neurodevelopmental disorders, several studies showed that a significant proportion of these genes converge on common pathways and protein networks. Here, we used a reversed approach, by screening the AnkyrinG protein-protein interaction network for genetic variation in a large cohort of 1009 cases with neurodevelopmental disorders. We identified a significant enrichment of de novo potentially disease-causing variants in this network, confirming that this protein network plays an important role in the emergence of several neurodevelopmental disorders.Subject terms: Genetics research, Neurological disorders  相似文献   
4.
In a number of pathogens, heat shock proteins (hsp) stimulate humoral and cellular immune responses despite significant sequence identity with host hsp. The 70-kD hsp of Mycobacterium leprae, which shares 47% identity with human hsp70 at the protein level, elicited a T cell response in most Myco. bovis (bacille Calmette-Guérin (BCG)) vaccinees as well as leprosy and tuberculosis patients and their contacts. In order to locate T cell epitopes, DNA fragments encoding portions of the 70-kD hsp were expressed in the vector pGEX-2T and tested for T cell reactivity in an in vitro proliferative assay. Cultures of peripheral blood mononuclear cells (PBMC) from BCG vaccinees indicated that the C-terminal half of the molecule contained multiple T cell epitopes, as the T cells from a majority of Myco. leprae hsp70-reactive individuals responded to C-344. Lower proportions of patients with paucibacillary leprosy (36%) and tuberculosis patients (16%) responded to C-344. The smaller C-142 fragment which includes the terminal 70 residues unique to Myco. leprae and is the target for the human antibody response elicited a cellular response in few patients and no vaccinees. In order to map T cell epitopes, two series of synthetic peptides encompassing the region 278-502 were prepared. Using overlapping 12mer and 20mer peptides, this region of the molecule was found to contain several potential T cell epitopes. The longer peptides gave a clearer indication of reactive sequences including regions of the molecule which were not identified with the 12mer peptides. Fine mapping of reactive peptide pools using the 12mer peptides identified two T cell epitopes. Although both were located in regions of the molecule shared with Myco. tuberculosis, one appeared to be cross-reactive with the equivalent human sequence, and thus has the potential to initiate autoimmune responses.  相似文献   
5.
6.
Folate deficiency may be associated with an increased risk of cancer at certain sites. There is a need to measure folate status and putative biomarkers of cancer risk in the same target tissue, or in surrogate tissues. A study was carried out to develop a method for the rapid measurement of folate in human buccal mucosa and lymphocytes and to evaluate the responsiveness of this measurement in both tissues to folic acid supplementation in healthy subjects, relative to conventional markers of folate status. Three hundred and twenty-three adults, ages between 20 and 60 years, were screened for RBC folate concentrations. Sixty-five subjects with red cell folate between 200 and 650 nmol/L participated in a randomized, double blind, placebo-controlled, folic acid (1.2 mg) intervention trial, lasting 12 weeks. As anticipated, a significant baseline correlation (r = 0.36, P < 0.01) was observed between red cell folate and plasma 5-methyltetrahydrofolate (5-MeTHF). Lymphocyte total folate was significantly associated with plasma 5-MeTHF (r = 0.28, P < 0.05) and plasma total homocysteine concentration (r = -0.34, P < 0.05). Buccal mucosa total folate showed no correlation with either red cell folate or 5-MeTHF, but was significantly associated with lymphocyte total folate (r = 0.35, P < 0.01). Supplementation elicited a significant increase in lymphocyte total folate (P < 0.01), and this was strongly associated with the increase in RBC total folate (P < 0.01) and plasma 5-MeTHF (P < 0.01). Buccal mucosa total folate was not influenced by folate supplementation. Methods have been developed for the rapid measurement of lymphocyte and buccal mucosal total folate. Lymphocyte folate is sensitive to folate intake and is reflected by plasma 5-MeTHF.  相似文献   
7.
Accurate 3-D surface segmentation is a challenging task in echocardiography because of the relatively low image quality. We introduce a new method for 3-D segmentation of the endocardium involving temporal decorrelation of echo signals originating from tissue and blood using radiofrequency (RF) signals acquired in 3-D Doppler mode. Temporal features were extracted in 3-D Doppler mode, where a sequence of RF lines is recorded for each image line. Each set of RF lines is highly correlated because of the high pulse repetition frequency. However, for high blood flow, the RF signals will decorrelate over time in contrast to the endocardium, which will remain relatively highly correlated over time. These decorrelation features permit differentiation between myocardial tissue and blood flow. We describe an implementation of a 3-D segmentation model in which temporal information is used as external constraint. The model was validated in a phantom and in vivo in healthy volunteers (n = 5). The phantom study revealed that the model successfully segmented the artificial blood lumen even for low flow velocity and illustrated the sensitivity of the segmentations to flow rate. In healthy volunteers, high Dice similarity indices indicate that 3-D segmentation of the endocardial border in vivo is feasible.  相似文献   
8.
9.
Intensive care unit syndrome: a dangerous misnomer   总被引:19,自引:0,他引:19  
The terms intensive care unit (ICU) syndrome and ICU psychosis have been used interchangeably to describe a cluster of psychiatric symptoms that are unique to the ICU environment. It is often postulated that aspects of the ICU, such as sleep deprivation and sensory overload or monotony, are causes of the syndrome. This article reviews the empirical support for these propositions. We conclude that ICU syndrome does not differ from delirium and that ICU syndrome is caused exclusively by organic stressors on the central nervous system. We argue further that the term ICU syndrome is dangerous because it impedes standardized communication and research and may reduce the vigilance necessary to promptly investigate and reverse the medical cause of the delirium. Directions for future research are suggested.  相似文献   
10.
Neutrophils are indispensable for clearing infections with the prominent human pathogen Staphylococcus aureus. Here, we report that S. aureus secretes a family of proteins that potently inhibits the activity of neutrophil serine proteases (NSPs): neutrophil elastase (NE), proteinase 3, and cathepsin G. The NSPs, but not related serine proteases, are specifically blocked by the extracellular adherence protein (Eap) and the functionally orphan Eap homologs EapH1 and EapH2, with inhibitory-constant values in the low-nanomolar range. Eap proteins are together essential for NSP inhibition by S. aureus in vitro and promote staphylococcal infection in vivo. The crystal structure of the EapH1/NE complex showed that Eap molecules constitute a unique class of noncovalent protease inhibitors that occlude the catalytic cleft of NSPs. These findings increase our insights into the complex pathogenesis of S. aureus infections and create opportunities to design novel treatment strategies for inflammatory conditions related to excessive NSP activity.Infections with the human pathogen Staphylococcus aureus constitute a major risk to human health. Although this bacterium harmlessly colonizes more than 30% of the population via the nose or skin, it causes severe morbidity and mortality upon invasion of deeper tissues (1). To avert these serious infections, neutrophils play an indispensable role (2). Neutrophil serine proteases (NSPs), including neutrophil elastase (NE), proteinase 3 (PR3), and cathepsin G (CG), are important for various neutrophil functions. Active NSPs are stored within the azurophilic granules (3), but upon neutrophil activation, they either enter the nucleus to regulate extracellular trap (NET) formation (4) or they are released into the extracellular milieu to kill certain bacteria (5), cleave bacterial virulence factors (5, 6), or regulate immune responses by cleaving chemokines and receptors (7). Recently, a fourth neutrophil serine protease, denoted NSP4, was identified (8).Given the central role of NSPs in neutrophil function, we wondered whether S. aureus had evolved mechanisms to cope with NSPs. In this study, we discover that S. aureus secretes a family of proteins that specifically and potently block NSPs: extracellular adherence protein (Eap) and the hitherto functional orphans Eap-homologue (EapH) 1 and 2. Structural studies presented here show that Eap molecules represent a unique class of noncovalent NSP inhibitors that is distinct from the well-known chelonianin class of inhibitors. These mechanistic insights can initiate development of novel, broad-range NSP inhibitors to be used in various inflammatory conditions. Furthermore, these insights increase our understanding of the pathogenicity of S. aureus and underline the exceptional capability of this pathogen to adapt to its host by modulating the immune response.  相似文献   
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号