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排序方式: 共有95条查询结果,搜索用时 31 毫秒
1.
Natalio Garbi Satoshi Tanaka Maries Van Den Broek Frank Momburg Günter J. Hmmerling 《Immunological reviews》2005,207(1):77-88
Summary: Assembly of major histocompatibility complex (MHC) class I molecules in the endoplasmic reticulum is a highly coordinated process that results in abundant class I/peptide complexes at the cell surface for recognition by CD8+ T cells and natural killer cells. During the assembly process, a number of chaperones and accessory molecules, such as transporter associated with antigen processing, tapasin, ER60, and calreticulin, assist newly synthesized class I molecules to facilitate loading of antigenic peptides and to optimize the repertoire of surface class I/peptide complexes. This review focuses on the relative importance of these accessory molecules for CD8+ T‐cell responses in vivo and discusses reasons that may help explain why some CD8+ T‐cell responses develop normally in mice deficient in components of class I assembly, despite impaired antigen presentation. 相似文献
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Clinical and immunological features of adult-onset generalized autoimmune gut disorder 总被引:1,自引:0,他引:1
León F Olivencia P Rodríguez-Pena R Sánchez L Redondo C Alvarez I Moreira V Roy G 《The American journal of gastroenterology》2004,99(8):1563-1571
OBJECTIVES: Autoimmune enteropathy is a rare disorder of unknown pathogenesis, characterized by protracted diarrhea, villous atrophy, and enterocyte autoantibodies. Its association with extended inflammation of the whole gastrointestinal tract is termed as generalized autoimmune gut disorder (GAGD), generally a pediatric disease of difficult management due to its association with immunodeficiency. The aim of our work is to describe the mucosal immunological basis of an adult-onset case of GAGD. METHODS: We studied an adult female with a severe inflammatory involvement of the gastrointestinal tract (stomach, small and large bowel, and liver) and antienterocyte autoantibodies. She had antibody deficiency and a predisposition to systemic autoimmunity. We analyzed, by immunohistochemistry and flow cytometry, the phenotypic and functional characteristics of her intestinal intraepithelial and lamina propria (LP) lymphocytes. RESULTS: We observed the prominent and constant presence of an unusual CD4+alphaE/beta7- Tc subset in the jejunal epithelium. Signs of the lymphocyte activation as well as the prominent lymphoid TNF-alpha production observed in the rectal mucosa support the involvement of a cell-mediated pro-inflammatory response in the pathogenesis of GAGD. CONCLUSIONS: We report the second case of an adult fulfilling all diagnostic criteria for GAGD. We propose that the activated LP CD4+ T lymphocytes, as well as those atypically located in the epithelium, may play a pathogenic role. The alphaE/beta7- IEL could constitute a diagnostic marker of intestinal autoimmunity in the cases when autoantibodies are not evidenced, and mucosal TNF-alpha might represent a novel therapeutic target in this severe disease. 相似文献
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Sanchez-Muñoz LB Santón A Cano A Lopez A Almeida J Orfao A Escribano L Roy G 《European journal of gastroenterology & hepatology》2008,20(5):478-487
The etiology of refractory celiac sprue (RCS) is unclear. In a high proportion of cases, the clonal nature of intestinal intraepithelial lymphocytes (IEL) can be demonstrated and a pathogenetic implication of intestinal IEL has been postulated. The prognosis of this subgroup of RCS is poor, with a high risk to develop an overt lymphoma and uncontrolled malabsorption despite steroid/immunosuppressive therapy. Cases with a relatively indolent clinical course, however, exist and their early diagnosis may be difficult. To gain insight into the pathogenic implication of intestinal IEL in refractory celiac sprue, we have performed an extensive phenotypic and functional characterization of clonal intestinal IEL in a patient with an indolent form of refractory celiac sprue, using multiparametric flow cytometry. The abnormal lymphocyte infiltrate lacked surface membrane expression of CD3/T-cell receptor (TCR) complexes (TCR(-), CD4(-), CD8(-), sCD3(-)), but contained intracellular CD3(epsilon) (CyCD3(+)) and surface CD103(+) and CD7(+). In particular, these cells showed a unique spontaneous ex-vivo cytokine secretion profile with an increased percentage of CD3(-) IEL containing TNF-alpha and IL-10, in the absence of IL-2, IL-4 and IFN-gamma. Altogether our results suggest that flow cytometry immunophenotyping of intestinal IEL, in cases suspected of celiac disease and their complicated forms, could be of great help in the correct diagnosis of RCS and the understanding of the immunopathogenic mechanisms of the disease and their clinical and/or therapeutical implications. 相似文献
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ER Stress During the Pubertal Growth Spurt Results in Impaired Long‐Bone Growth in Chondrocyte‐Specific ERp57 Knockout Mice
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Andrea Linz Yvonne Knieper Tobias Gronau Uwe Hansen Attila Aszodi Natalio Garbi Günter J Hämmerling Thomas Pap Peter Bruckner Rita Dreier 《Journal of bone and mineral research》2015,30(8):1481-1493
Long‐bone growth by endochondral ossification is cooperatively accomplished by chondrocyte proliferation, hypertrophic differentiation, and appropriate secretion of collagens, glycoproteins, and proteoglycans into the extracellular matrix (ECM). Before folding and entering the secretory pathway, ECM macromolecules in general are subject to extensive posttranslational modification, orchestrated by chaperone complexes in the endoplasmic reticulum (ER). ERp57 is a member of the protein disulfide isomerase (PDI) family and facilitates correct folding of newly synthesized glycoproteins by rearrangement of native disulfide bonds. Here, we show that ERp57‐dependent PDI activity is essential for postnatal skeletal growth, especially during the pubertal growth spurt characterized by intensive matrix deposition. Loss of ERp57 in growth plates of cartilage‐specific ERp57 knockout mice (ERp57 KO) results in ER stress, unfolded protein response (UPR), reduced proliferation, and accelerated apoptotic cell death of chondrocytes. Together this results in a delay of long‐bone growth with the following characteristics: (1) enlarged growth plates; (2) expanded hypertrophic zones; (3) retarded osteoclast recruitment; (4) delayed remodeling of the proteoglycan‐rich matrix; and (5) reduced numbers of bone trabeculae. All the growth plate and bone abnormalities, however, become attenuated after the pubertal growth spurt, when protein synthesis is decelerated and, hence, ERp57 function is less essential. © 2015 American Society for Bone and Mineral Research. 相似文献
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D Metras B Kreitmann A Vaillant M Noirclerc M Benichou G Habib A Serradimigni A Pannetier J P Couvely O Garbi 《Archives des maladies du coeur et des vaisseaux》1990,83(2):209-215
Since December 1985, we have performed 38 transplantations: cardiac (CT) n: 31, cardiopulmonary (CPT) n: 1, or bipulmonary (BPT) n: 6. There were 31 male and 7 female patients, aged 7 to 62, mean 46. In the cardiac group, the cardiomyopathy was primitive in 13, ischemic in 16, valvular in 2. Five patients had undergone one or more previous operations. Three patients had a biventricular assist device (1,6 and 7 days before transplant) for acute cardiac failure. The indication of CPT or BPT was pulmonary artery hypertension (1), silicosis (1), cystic fibrosis (4). There were 4 post-operative deaths in the CT group (12.9%); failure of graft, low cardiac output, pulmonary artery hypertension by multiple pulmonary thrombosis, and 2 deaths in the CPT and BPT groups (28%). The mean post-operative hospital stay was one month. All patients with CT were treated by an initial maintenance bitherapy protocol (cyclosporine, steroids) and observed by myocardial biopsies and echocardiograms. In 40 per cent of the patients, Azathioprine was subsequently added. The patients had 2.1 rejection episode/patient/year, either spontaneously reversed of treated medically. There were two late deaths (2 and 7 months) by refractory rejection. 78 per cent of the patients were alive one year after transplant. All survivors have recovered a normal life, some of them with full-time work.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
9.
Antigen presentation by MHC class I molecules is necessary for CD8 T-cell activation. Optimal peptide loading onto MHC class I molecules occurs mainly in the peptide-loading complex in the endoplasmic reticulum. The identification of a covalent association between the thiol oxidoreductase ERp57 and tapasin, and its impact on the loading complex, are important recent developments in this field of research. In the absence of ERp57, the recruitment of MHC class I molecules into this complex by tapasin is greatly impaired both in the number of molecules and in their interaction time, suggesting a key structural role for the ERp57-tapasin association in the peptide-loading complex. The role of ERp57 as a thiol oxidoreductase in the peptide-loading complex remains, however, controversial and further research regarding this subject is required. 相似文献
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