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31.
Molecular and immunological evaluation of the expression of cancer/testis gene products in human colorectal cancer 总被引:1,自引:0,他引:1
Alves PM Lévy N Bouzourene H Viatte S Bricard G Ayyoub M Vuilleumier H Givel JC Halkic N Speiser DE Romero P Lévy F 《Cancer immunology, immunotherapy : CII》2007,56(6):839-847
Tumor-specific gene products, such as cancer/testis (CT) antigens, constitute promising targets for the development of T cell
vaccines. Whereas CT antigens are frequently expressed in melanoma, their expression in colorectal cancers (CRC) remains poorly
characterized. Here, we have studied the expression of the CT antigens MAGE-A3, MAGE-A4, MAGE-A10, NY-ESO-1 and SSX2 in CRC
because of the presence of well-described HLA-A2-restricted epitopes in their sequences. Our analyses of 41 primary CRC and
14 metastatic liver lesions confirmed the low frequency of expression of these CT antigens. No increased expression frequencies
were observed in metastatic tumors compared to primary tumors. Histological analyses of CRC samples revealed heterogeneous
expression of individual CT antigens. Finally, evidence of a naturally acquired CT antigen-specific CD8+ T cell response could be demonstrated. These results show that the expression of CT antigens in a subset of CRC patients
induces readily detectable T cell responses. 相似文献
32.
Godefroy E Wang Y Souleimanian NE Scotto L Stevanovic S Chen YT Valmori D Ayyoub M 《Cancer immunology, immunotherapy : CII》2007,56(8):1183-1192
Proteins encoded by genes of the SSX family are specifically expressed in tumors and are therefore relevant targets for cancer immunotherapy. One of the first identified family members, SSX-1, is expressed in a large fraction of synovial sarcomas as a fusion protein together with the product of the SYT gene. In addition, the full-length SSX-1 antigen is frequently expressed in tumors of several other histological types such as sarcoma, melanoma, hepatocellular carcinoma, ovarian cancer and myeloma. To date, however, SSX-1 specific T cell responses have not been investigated and no SSX-1 derived T cell epitopes have been described. Here, we have assessed the presence of CD4(+) T cells directed against the SSX-1 antigen in circulating lymphocytes of cancer-free individuals. After a single in vitro stimulation with a pool of peptides spanning the entire SSX-1 protein we could detect and isolate SSX-1-specific CD4(+) T cells from 5/5 donors analyzed. SSX-1-specific polyclonal populations isolated from these cultures recognized peptides located in three distinct regions of the protein containing clusters of sequences with significant predicted binding to frequently expressed MHC class II alleles. Characterization of specific clonal CD4(+) T cell populations derived from one donor allowed the identification of several naturally processed epitopes recognized in association with HLA-DR. These data document the existence of a significant repertoire of CD4(+) T cells specific for SSX-1 derived sequences in circulating lymphocytes of any individual that can be exploited for the development of both passive and active immunotherapeutic approaches to control disease evolution in cancer patients. 相似文献
33.
Kammoun-Krichen M Bougacha-Elleuch N Makni K Rebai M Peraldi-Roux S Rebai A Mnif M Abid M Jouida J Ayadi H 《European cytokine network》2007,18(4):196-200
Autoimmune thyroid diseases (AITDs), including Graves' disease (GD) and autoimmune hypothyroidism (AH), are inherited as complex traits. Among the genes contributing to AITDs susceptibility are genes of the IL-1 family. IL-1 regulates T and B lymphocyte maturation, including the induction of several cytokines and cytokine receptors. Therefore, disturbances of this balance may not only play a role in inflammation but also in the pathogenesis of autoimmunity. In order to investigate genetic association of IL-1 gene polymorphisms with AITDs, we performed both a familial study in a large Tunisian pedigree with high prevalence of AITDs (64 patients and 176 controls), and a case-control study (131 GD unrelated patients and 225 healthy controls). PCR and PCR-RFLP methods were used to analyse respectively a VNTR in the IL-1RN gene and three SNPs in both IL-1B genes (-511 C/T and +3954 C/T) and IL-1A (-889 C/T). The family-based association study showed an association of the IL-1B+3954 C/T polymorphism (p=0.02) and two haplotypes IL-1RN*3/C/T/T and IL-1RN*1/C/T/T (p=0.009 and p=0.047 respectively) with AITDs. The case-control study is the first study revealing a significant association of the IL-1A-889 C/T polymorphism (chi2=10.23; p=0.0014) with susceptibility to GD. Our data suggest that the IL-1 gene cluster may harbour susceptibility genes for AITDs and GD pathogenesis in the Tunisian population. 相似文献
34.
A new hepatoprotective flavone glycoside from the flowers of Onopordum alexandrinum growing in Egypt
Salama MM Ezzat SM Sleem AA 《Zeitschrift für Naturforschung. C, Journal of biosciences》2011,66(5-6):251-259
A bioactivity-guided fractionation of the ethyl acetate fraction of the flowers of Onopordum alexandrinum L. (Asteraceae) yielded a new flavonoidal glycoside designated as acacetin-7-O-galacturonide (9), alongside with nine known flavonoids; 6-methoxy-apigenin (hispidulin) (1), acacetin (2), apigenin (3), luteolin (4), kaempferol (5), eriodictyol (6), apigenin-7-O-glucoside (7), luteolin-7-O-glucoside (8), and kaempferol-3-O-rutinoside (10). The compounds were assayed for their hepatoprotective activity against CCl4-induced hepatic cell damage in rats and free radical scavenging activity using 2,2-diphenyl-1-picrylhydrazyl (DPPH). Compounds 4, 6, 9, and 10 have not been previously reported from flowers of O. alexandrinum L., and this is the first report of acacetin-7-O-galacturonide (9) in nature which has also shown significant hepatoprotective and free radical scavenging effects. The isolated compounds were identified using different spectroscopic methods (UV, 1H NMR, 13C NMR, HMQC, HMBC, and COSY). 相似文献
35.
Houssen ME Haron MM Metwally SS Ibrahim TM 《Journal of physiology and biochemistry》2011,67(1):115-120
Atherosclerosis is a chronic disease of the arterial wall where both innate and adaptive immuno-inflammatory mechanisms are
involved. Inflammatory cytokines are implicated in the development and progression of atherosclerotic lesions. Immunomodulatory
therapies have been proposed for the treatment of atherosclerosis. Therefore, the aim of this study was to investigate the
systemic anti-inflammatory and immunomodulatory effects of atorvastatin, cyclosporine A (CsA), and tacrolimus (FK506) on plasma
inflammatory markers in atherosclerotic rabbits. Male New Zealand rabbits were randomized into five groups each of 12 animals.
Standard diet-fed group served as control, and the cholesterol-fed group received a diet supplemented with 1% cholesterol
alone, cholesterol + atorvastatin, cholesterol + FK506, and cholesterol + CsA. Serum levels of lipid profile parameters (triglycerides,
cholesterol, and high-density lipoprotein) were measured using colorimetric methods. Serum levels of C-reactive protein (CRP),
interleukin-6 (Il-6), and interferon-gamma (INF-γ) were measured in all studied groups using ELISA techniques. Our results
revealed a significant decrease (p < 0.001) in the serum levels of lipid profile parameters, CRP, Il-6, and INF-γ in atorvastatin-treated group compared with
the cholesterol-fed group. On the other hand, a non-significant difference was observed for the same parameters in either
FK506- or CsA-treated groups compared with the cholesterol-fed group. In conclusion, atorvastatin has a systemic anti-inflammatory
role that far surpassed the cholesterol reduction effect alone. FK506 or CsA failed to suppress elevated plasma inflammatory
markers. Thus, low doses of these two immunomodulating drugs could not have generalized systemic anti-inflammatory or immunosuppressive
effects. 相似文献
36.
37.
Hamaï A Duperrier-Amouriaux K Pignon P Raimbaud I Memeo L Colarossi C Canzonieri V Perin T Classe JM Campone M Jézéquel P Campion L Ayyoub M Valmori D 《PloS one》2011,6(6):e21129
The highly immunogenic human tumor antigen NY-ESO-1 (ESO) is a target of choice for anti-cancer immune therapy. In this study, we assessed spontaneous antibody (Ab) responses to ESO in a large cohort of patients with primary breast cancer (BC) and addressed the correlation between the presence of anti-ESO Ab, the expression of ESO in the tumors and their characteristics. We found detectable Ab responses to ESO in 1% of the patients. Tumors from patients with circulating Ab to ESO exhibited common characteristics, being mainly hormone receptor (HR)− invasive ductal carcinomas of high grade, including both HER2− and HER2+ tumors. In line with these results, we detected ESO expression in 20% of primary HR− BC, including both ESO Ab+ and Ab− patients, but not in HR+ BC. Interestingly, whereas expression levels in ESO+ BC were not significantly different between ESO Ab+ and Ab− patients, the former had, in average, significantly higher numbers of tumor-infiltrated lymph nodes, indicating that lymph node invasion may be required for the development of spontaneous anti-tumor immune responses. Thus, the presence of ESO Ab identifies a tumor subtype of HR− (HER2− or HER2+) primary BC with frequent ESO expression and, together with the assessment of antigen expression in the tumor, may be instrumental for the selection of patients for whom ESO-based immunotherapy may complement standard therapy. 相似文献
38.
Periklis?Makrythanasis Michel?Guipponi Federico?A.?Santoni Maha?Zaki Mahmoud?Y.?Issa Muhammad?Ansar Hanan?HamamyEmail author Stylianos?E.?AntonarakisEmail author 《Human genomics》2016,10(1):26
Background
The recent availability of whole-exome sequencing has opened new possibilities for the evaluation of individuals with genetically undiagnosed intellectual disability.Results
We report two affected siblings, offspring of first-cousin parents, with intellectual disability, hypotonia, short stature, growth hormone deficiency, and delayed bone age. All members of the nuclear family were genotyped, and exome sequencing was performed in one of the affected individuals. We used an in-house algorithm (CATCH v1.1) that combines homozygosity mapping with exome sequencing results and provides a list of candidate variants. One identified novel homozygous missense variant in KALRN (NM_003947.4:c.3644C>A: p.(Thr1215Lys)) was predicted to be pathogenic by all pathogenicity prediction software used (SIFT, PolyPhen, Mutation Taster). KALRN encodes the protein kalirin, which is a GTP-exchange factor protein with a reported role in cytoskeletal remodeling and dendritic spine formation in neurons. It is known that mice with ablation of Kalrn exhibit age-dependent functional deficits and behavioral phenotypes.Conclusion
Exome sequencing provided initial evidence linking KALRN to monogenic intellectual disability in man, and we propose that KALRN is the causative gene for the autosomal recessive phenotype in this family.39.
40.