全文获取类型
收费全文 | 107篇 |
免费 | 30篇 |
专业分类
儿科学 | 2篇 |
妇产科学 | 2篇 |
基础医学 | 22篇 |
口腔科学 | 4篇 |
临床医学 | 14篇 |
内科学 | 17篇 |
神经病学 | 8篇 |
特种医学 | 8篇 |
外科学 | 4篇 |
综合类 | 24篇 |
预防医学 | 7篇 |
眼科学 | 2篇 |
药学 | 3篇 |
肿瘤学 | 20篇 |
出版年
2019年 | 1篇 |
2014年 | 2篇 |
2013年 | 3篇 |
2012年 | 2篇 |
2011年 | 3篇 |
2010年 | 3篇 |
2009年 | 4篇 |
2008年 | 2篇 |
2007年 | 5篇 |
2006年 | 3篇 |
2005年 | 8篇 |
2004年 | 9篇 |
2003年 | 4篇 |
2002年 | 7篇 |
2001年 | 5篇 |
2000年 | 6篇 |
1999年 | 2篇 |
1998年 | 1篇 |
1997年 | 1篇 |
1996年 | 6篇 |
1995年 | 6篇 |
1994年 | 4篇 |
1993年 | 4篇 |
1992年 | 2篇 |
1989年 | 5篇 |
1987年 | 6篇 |
1986年 | 3篇 |
1985年 | 3篇 |
1984年 | 3篇 |
1983年 | 3篇 |
1982年 | 7篇 |
1980年 | 1篇 |
1979年 | 1篇 |
1978年 | 2篇 |
1977年 | 1篇 |
1972年 | 1篇 |
1971年 | 1篇 |
1970年 | 1篇 |
1969年 | 2篇 |
1966年 | 1篇 |
1954年 | 1篇 |
1940年 | 1篇 |
1928年 | 1篇 |
排序方式: 共有137条查询结果,搜索用时 15 毫秒
71.
Use of specific antibody to demonstrate glycocalyx, K99 pili, and the spatial relationships of K99+ enterotoxigenic Escherichia coli in the ileum of colostrum-fed calves. 总被引:7,自引:10,他引:7
下载免费PDF全文
![点击此处可从《Infection and immunity》网站下载免费的PDF全文](/ch/ext_images/free.gif)
The attachment of enterotoxigenic Escherichia coli (ETEC) strain B44 (O9:K30:K99:F41:H-) to the ileal epithelium of newborn colostrum-fed calves was studied by electron microscopy. Stabilization of the bacterial glycocalyx (K30) and pili (K99) by fixation of tissue sections in specific antibody and staining with ruthenium red were used so that the bacterial surface structures could be clearly visualized and their spatial relationship to the intestinal brush border defined. When sections of ileum from infected calves were neither fixed in antibody nor stained with ruthenium red, the ETEC cells colonizing the small intestine were separated from each other and from the brush border by an electron-translucent halo; neither the glycocalyx nor the pili could be clearly resolved. When ruthenium red staining was used, the halo was partially filled by a net of electron-dense fibers composed of pili and condensed glycocalyx which extended to the brush border. Tissue sections reacted with anti-K30 antibody before staining with ruthenium red revealed microcolonies of ETEC surrounded by a discrete electron-dense glycocalyx 0.3 to 1.0 micrometers thick and in tight contact with the epithelial cell surface. When ileal tissue was treated with K99 antibody, the K99 pili were visible as discrete fibers extending from the bacterial cell surface through the glycocalyx. We discuss the role of these cell surface components in pathogenic adhesion and in the formation of protected microcolonies at the surface of the infected ileal epithelium. 相似文献
72.
The monocyte chemoattractant protein-1 (MCP-1)/CC-chemokine receptor 2 (CCR2) pathway plays a critical role in the development of antiglomerular basement membrane (anti-GBM) nephritis. We recently showed angiotensin II (Ang II) infusion in rats activated MCP-1 and transforming growth factor-β1 (TGF-β1), which in turn induced macrophage infiltration of renal tissues. This study was performed to demonstrate that combination therapy with a CCR2 antagonist (CA) and an Ang II type 1 receptor blocker (ARB) ameliorated renal injury in the anti-GBM nephritis model. An anti-GBM nephritis rat model developed progressive proteinuria and glomerular crescent formation, accompanied by increased macrophage infiltration and glomerular expression of MCP-1, angiotensinogen, Ang II, and TGF-β1. Treatment with CA alone or ARB alone moderately ameliorated kidney injury; however, the combination treatment with CA and ARB dramatically prevented proteinuria and markedly reduced glomerular crescent formation. The combination treatment also suppressed the induction of macrophage infiltration, MCP-1, angiotensinogen, Ang II, and TGF-β1 and reversed the fibrotic change in the glomeruli. Next, primary cultured glomerular mesangial cells (MCs) stimulated by Ang II showed significant increases in MCP-1 and TGF-β1 expression. Furthermore, cocultured model consisting of MCs, parietal epithelial cells, and macrophages showed an increase in Ang II-induced cell proliferation and collagen secretion. ARB treatment attenuated these augmentations. These data suggest that Ang II enhances glomerular crescent formation of anti-GBM nephritis. Moreover, our results demonstrate that inhibition of the MCP-1/CCR2 pathway with a combination of ARB effectively reduces renal injury in anti-GBM nephritis. 相似文献
73.
The hypothesis proposed is that anorexia nervosa (AN) is an autoimmune disease caused by delayed exposure to common micro-organisms in which auto-antibodies to regulatory peptides and hypothalamic neurons, which cross react with microbial antigens, disturb appetite and lead to decreased intake of food. IgG, IgA and IgM auto-antibodies to a range of regulatory peptides concerned with appetite and mood are found in patients with AN. The regulatory peptides show sequence homology with common micro-organisms of the microbial flora. Auto-antibodies to α melanocyte stimulating hormone (αMSH) are positively correlated with AN psychopathology. But patients with bulimia nervosa (BN) and normal healthy controls also have a similar range of auto-antibodies at comparable levels. The incidence of AN is rising in developed countries, the disease is more common in females than in males, the peak incidence is in the teenage years, there is seasonal variation in the month of birth and the disease is more common in higher socio-economic groups. These are all features which are consistent with the hygiene hypothesis. But there is no evidence that the disease is more common in first born than in later born children. There is a paucity of data on early life events such as attendance at nursery and exposure to pets. Genetic factors are important but the data on major histocompatibility complex (MHC) gene polymorphisms are contradictory. The epidemiological and serological data are consistent with the hypothesis under investigation but key questions in relation to the hygiene hypothesis have not been posed. A large case control study of AN epidemiology is indicated. MHC gene polymorphisms should be assessed. There is, however, sufficient evidence to justify a trial of pooled immunoglobulin therapy in patients with life threatening AN. 相似文献
74.
J E Sims R B Acres C E Grubin C J McMahan J M Wignall C J March S K Dower 《Proceedings of the National Academy of Sciences of the United States of America》1989,86(22):8946-8950
cDNA clones of the interleukin 1 (IL-1) receptor expressed in a human T-cell clone have been isolated by using a murine IL-1 receptor cDNA as a probe. The human and mouse receptors show a high degree of sequence conservation. Both are integral membrane proteins possessing a single membrane-spanning segment. Similar to the mouse receptor, the human IL-1 receptor contains a large cytoplasmic region and an extracellular, IL-1 binding portion composed of three immunoglobulin-like domains. When transfected into COS cells, the human IL-1 receptor cDNA clone leads to expression of two different affinity classes of receptors, with Ka values indistinguishable from those determined for IL-1 receptors in the original T-cell clone. An IL-1 receptor expressed in human dermal fibroblasts has also been cloned and sequenced and found to be identical to the IL-1 receptor expressed in T cells. 相似文献
75.
Dreicer R Stadler WM Ahmann FR Whiteside T Bizouarne N Acres B Limacher JM Squiban P Pantuck A 《Investigational new drugs》2009,27(4):379-386
Summary
Purpose: TG4010 is a recombinant MVA vector expressing the tumor-associated antigen MUC1 and IL2. We explored the effect two schedules
of TG4010 on PSA in men with PSA progression. Patients and methods: A randomized phase II trial was conducted in 40 patients with PSA progression. Patients had PSA doubling times less than
10 months, with no overt evidence of disease. Patients received either weekly subcutaneous injection (sc) of TG4010 108 pfu for 6 weeks, then one injection every 3 weeks or sc injection of TG4010 108 pfu every 3 weeks. Results: The primary endpoint of a 50% decrease in PSA values from baseline was not observed. Nevertheless, 13 of 40 patients had
a more than two fold improvement in PSA doubling time. Ten patients had their PSA stabilized for over 8 months. Therapy was
well tolerated. Conclusions: Although the primary endpoint was not achieved, there is evidence of biologic activity of TG4010 in patients with PSA progression,
further investigation in prostate cancer is warranted. 相似文献
76.
Tumor-associated antigens (TAAs) have been formulated into vaccines that, combined with adjuvants, cytokines or other strategies to boost the immune response, are now in clinical development. Both humoral and cellular immune responses to TAAs have been generated using these vaccines. This approach relies on the patient's own immune system generating an effective anti-tumor immune response. The advantage of this over therapy with monoclonal antibodies for the treatment of cancer is that multiple antigenic epitopes can be involved and the immune system is able to adapt to the most effective antigenic specificity for tumor growth control and rejection. In this article, we describe the clinical use of vaccinia virus, in particular modified vaccinia virus Ankara (MVA), to express TAAs in vivo and to stimulate an effective immune response to the cancer antigens. 相似文献
77.
Tyler LK Stamatakis EA Bright P Acres K Abdallah S Rodd JM Moss HE 《Journal of cognitive neuroscience》2004,16(3):351-362
How objects are represented and processed in the brain is a central topic in cognitive neuroscience. Previous studies have shown that knowledge of objects is represented in a feature-based distributed neural system primarily involving occipital and temporal cortical regions. Research with nonhuman primates suggest that these features are structured in a hierarchical system with posterior neurons in the inferior temporal cortex representing simple features and anterior neurons in the perirhinal cortex representing complex conjunctions of features (Bussey & Saksida, 2002; Murray & Bussey, 1999). On this account, the perirhinal cortex plays a crucial role in object identification by integrating information from different sensory systems into more complex polymodal feature conjunctions. We tested the implications of these claims for human object processing in an event-related fMRI study in which we presented colored pictures of common objects for 19 subjects to name at two levels of specificity - basic and domain. We reasoned that domain-level naming requires access to a coarser-grained representation of objects, thus involving only posterior regions of the inferior temporal cortex. In contrast, basic-level naming requires finer-grained discrimination to differentiate between similar objects, and thus should involve anterior temporal regions, including the perirhinal cortex. We found that object processing always activated the fusiform gyrus bilaterally, irrespective of the task, whereas the perirhinal cortex was only activated when the task required finer-grained discriminations. These results suggest that the same kind of hierarchical structure, which has been proposed for object processing in the monkey temporal cortex, functions in the human. 相似文献
78.
79.
Pantuck AJ van Ophoven A Gitlitz BJ Tso CL Acres B Squiban P Ross ME Belldegrun AS Figlin RA 《Journal of immunotherapy (Hagerstown, Md. : 1997)》2004,27(3):240-253
MUC-1 is overexpressed on many tumor cells. In addition, aberrant glycosylation of MUC-1 on human tumors leads to exposure of cryptic peptide epitopes that play a role in tumor immunity. As such, it has been identified as a potential target for immunotherapy. The purpose of this phase 1 clinical trial was to determine the maximum tolerated dose, safety of a multiple-dose regimen, and the immunologic effect of vaccinia virus expressing MUC-1 and IL-2 genes (VV/MUC-1/IL-2) in patients with advanced prostate cancer. Five x 10(5), 5 x 10(6), and 5 x 10(7) plaque-forming units (pfu) of vaccinia viruses were used in the dose-escalating study. Viruses were given via intramuscular injection, and clinical response and immune function modulation were analyzed. No grade 3 or 4 toxicity was observed. Objective clinical response was observed after the fourth injection (0.3 ng/mL) in only one patient who received an intermediate dose of virus. Systemic immune modulation in this patient included (1) up-regulation of IL-2 (CD25) and T cell (TcR alphabeta) receptors, (2) increase in the CD4/CD8 ratio (2.5-fold) (3) augmentation of T-helper type 1 cell (TH1) (interferon-gamma and tumor necrosis factor-alpha) but not TH2 (IL-4) cytokine mRNA expression, (4) induction of natural killer cell activity and MHC independent MUC-1 specific cytotoxic T-cell activity, and (5) normalization of mRNA expression of T-cell-associated signal transduction molecules TcR-zeta and p56lck. These results suggest that VV/MUC-1/IL-2 gene therapy with a maximum tolerated dose of 5 x 10(7) pfu is safe and well tolerated. 相似文献
80.