全文获取类型
收费全文 | 123篇 |
免费 | 10篇 |
出版年
2021年 | 1篇 |
2019年 | 1篇 |
2018年 | 1篇 |
2017年 | 2篇 |
2016年 | 5篇 |
2014年 | 7篇 |
2013年 | 5篇 |
2012年 | 6篇 |
2011年 | 10篇 |
2010年 | 7篇 |
2009年 | 3篇 |
2008年 | 6篇 |
2007年 | 11篇 |
2006年 | 11篇 |
2005年 | 2篇 |
2004年 | 6篇 |
2003年 | 4篇 |
2002年 | 7篇 |
2001年 | 4篇 |
2000年 | 1篇 |
1999年 | 1篇 |
1998年 | 1篇 |
1997年 | 1篇 |
1996年 | 1篇 |
1994年 | 2篇 |
1993年 | 3篇 |
1992年 | 3篇 |
1990年 | 1篇 |
1989年 | 2篇 |
1988年 | 1篇 |
1987年 | 1篇 |
1985年 | 1篇 |
1984年 | 2篇 |
1983年 | 4篇 |
1982年 | 2篇 |
1981年 | 2篇 |
1980年 | 2篇 |
1977年 | 2篇 |
1969年 | 1篇 |
排序方式: 共有133条查询结果,搜索用时 15 毫秒
91.
Theurillat JP Zürrer-Härdi U Varga Z Storz M Probst-Hensch NM Seifert B Fehr MK Fink D Ferrone S Pestalozzi B Jungbluth AA Chen YT Jäger D Knuth A Moch H 《Cancer immunology, immunotherapy : CII》2007,56(11):1723-1731
NY-BR-1 is a recently identified differentiation antigen of the mammary gland. To use NY-BR-1 for T-cell-based immunotherapy, analysis of its co-expression with HLA class I antigens is required. In the present tissue microarray study, primary breast cancers (n = 1,444), recurrences (n = 88), lymph node (n = 525) and distant metastases (n = 91) were studied for NY-BR-1 expression using a novel monoclonal antibody. NY-BR-1 expression was compared with prognosis, estrogen receptor, HER2-status, EGFR and HLA class I antigen expression. NY-BR-1 was more frequently expressed in grade 1 (82%) than in grade 2 (69%) and grade 3 (46%) carcinomas (P < 0.0001). Moreover, NY-BR-1 expression correlated directly with estrogen receptor expression (P < 0.0001) and inversely correlated with HER2-status and EGFR expression (P < 0.0001 for both). Considering high expression level of co-expression, 198/1,321 (15%) primary breast carcinomas and 4/65 (6%) distant metastases expressed NY-BR-1 and HLA class I, suggesting that active immunotherapy can be applied to about 10% of breast cancer patients. Survival analysis showed an association of NY-BR-1 expression with better patient outcome (P = 0.015). No difference between NY-BR-1 expression of primary tumors and metastases could be found, indicating that the presence of NY-BR-1 in metastases can be deduced from their corresponding primary. Forty-three paired biopsies taken from patients before and after chemotherapy suggest that NY-BR-1 expression is not influenced by preceding chemotherapy (kappa = 0.89, P < 0.0001). In summary, the co-expression of NY-BR-1 with HLA class I antigens and its expression in metastases without modification by chemotherapy suggest that NY-BR-1 targeted immunotherapy represents a viable strategy in addition to other targeted cancer drug therapies of breast cancer. 相似文献
92.
Zubieta C Krishna SS McMullan D Miller MD Abdubek P Agarwalla S Ambing E Astakhova T Axelrod HL Carlton D Chiu HJ Clayton T Deller M DiDonato M Duan L Elsliger MA Grzechnik SK Hale J Hampton E Han GW Haugen J Jaroszewski L Jin KK Klock HE Knuth MW Koesema E Kumar A Marciano D Morse AT Nigoghossian E Oommachen S Reyes R Rife CL van den Bedem H Weekes D White A Xu Q Hodgson KO Wooley J Deacon AM Godzik A Lesley SA Wilson IA 《Proteins》2007,68(4):999-1005
93.
Nadja Ristagno Alexander Knuth Bernhard C Pestalozzi 《International Seminars in Surgical Oncology : ISSO》2007,4(1):26
Background
Biliary cancer includes cancer of the gallbladder as well as extrahepatic and intrahepatic cholangiocarcinoma. Surgery is the only curative treatment option available. Recently, much more aggressive surgical approaches have been employed. Therefore, we have investigated outcome of biliary cancer before and after establishment of an aggressive surgical approach.Methods
Retrospective single-center analysis comparing two time periods of 5 years each. During the second period new surgical expertise and a much more aggressive surgical approach were used.Results
In the first time period (5/1995–4/2000) only 29 patients with biliary cancer were treated at our institution, while a total of 85 patients were treated during the second time period (5/2000–4/2005). Surgical resection was attempted in 55% during the first period versus 62% in the second; resection was complete in 37.5% and 58.5%, respectively. Patients undergoing resection during the second time period were more likely to be without relapse compared with patients undergoing resection in the first time period. No patient from the first period is without evidence of disease, compared to 11 patients operated in the second period. Resected patients had better survival compared with unresected patients for all tumor locations (gallbladder, extrahepatic and intrahepatic cholangiocarcinomas). Overall survival of patients was not significantly different between patients treated during the first versus the second time period.Conclusion
In patients with biliary cancer surgical resection should be attempted whenever possible. However, long-term survival can be achieved only when a complete resection is obtained.94.
The relationship of contraceptive history to diagnostic category of amenorrhoea was analysed in 131 consecutively investigated cases of secondary amenorrhoea. Amenorrhoea occurred in 52 patients immediately after discontinuing the oral contraceptive. Twenty-two had had amenorrhoea before oral contraceptive treatment and 23 patients before the episode of non-contraceptive-related amenorrhoea investigated here. When these cases were excluded from analysis there was no significant difference in the distribution of any of the diagnostic categories between those who had used the oral contraceptive and those who had not. The results suggest that using oral contraceptives does not cause subsequent amenorrhoea. 相似文献
95.
Erratum: Metabolic adaptation following massive weight loss is related to the degree of energy imbalance and changes in circulating leptin
下载免费PDF全文
![点击此处可从《Obesity (Silver Spring, Md.)》网站下载免费的PDF全文](/ch/ext_images/free.gif)
96.
Spontaneous CD8 T cell responses against the melanocyte differentiation antigen RAB38/NY-MEL-1 in melanoma patients 总被引:3,自引:0,他引:3
Walton SM Gerlinger M de la Rosa O Nuber N Knights A Gati A Laumer M Strauss L Exner C Schäfer N Urosevic M Dummer R Tiercy JM Mackensen A Jaeger E Lévy F Knuth A Jäger D Zippelius A 《Journal of immunology (Baltimore, Md. : 1950)》2006,177(11):8212-8218
The melanocyte differentiation Ag RAB38/NY-MEL-1 was identified by serological expression cloning (SEREX) and is expressed in the vast majority of melanoma lesions. The immunogenicity of RAB38/NY-MEL-1 has been corroborated previously by the frequent occurrence of specific Ab responses in melanoma patients. To elucidate potential CD8 T cell responses, we applied in vitro sensitization with overlapping peptides spanning the RAB38/NY-MEL-1 protein sequence and the reverse immunology approach. The identified peptide RAB38/NY-MEL-1(50-58) exhibited a marked response in ELISPOT assays after in vitro sensitization of CD8 T cells from HLA-A *0201(+) melanoma patients. In vitro digestion assays using purified proteasomes provided evidence of natural processing of RAB38/NY-MEL-1(50-58) peptide. Accordingly, monoclonal RAB38/NY-MEL-1(50-58)-specific T cell populations were capable of specifically recognizing HLA-A2(+) melanoma cell lines expressing RAB38/NY-MEL-1. Applying fluorescent HLA-A2/RAB38/NY-MEL-1(50-58) multimeric constructs, we were able to document a spontaneously developed memory/effector CD8 T cell response against this peptide in a melanoma patient. To elucidate the Ag-processing pathway, we demonstrate that RAB38/NY-MEL-1(50-58) is produced efficiently by the standard proteasome and the immunoproteasome. In addition to the identification of a RAB38/NY-MEL-1-derived immunogenic CD8 T cell epitope, this study is instrumental for both the onset and monitoring of future RAB38/NY-MEL-1-based vaccination trials. 相似文献
97.
Lars Hagmar Stefano Bonassi Ulf Strömberg Zoli Mikoczy Cecilia Lando Inger-Lise Hansteen Alicia Huici Montagud Lisbeth Knudsen Hannu Norppa Christina Reuterwall Håkan Tinnerberg Anton Brøgger Alessandra Forni Benkt Högstedt Bo Lambert Felix Mitelman Ingrid Nordenson Sisko Salomaa Staffan Skerfving 《Mutation research》1998,405(2):235-178
The cytogenetic endpoints in peripheral blood lymphocytes: chromosomal aberrations (CA), sister chromatid exchange (SCE) and micronuclei (MN) are established biomarkers of exposure for mutagens or carcinogens in the work environment. However, it is not clear whether these biomarkers also may serve as biomarkers for genotoxic effects which will result in an enhanced cancer risk. In order to assess this problem, Nordic and Italian cohorts were established, and preliminary results from these two studies indicated a predictive value of CA frequency for cancer risk, whereas no such associations were observed for SCE or MN. A collaborative study between the Nordic and Italian research groups, will enable a more thorough evaluation of the cancer predictivity of the cytogenetic endpoints. We here report on the establishment of a joint data base comprising 5271 subjects, examined 1965–1988 for at least one cytogenetic biomarker. Totally, 3540 subjects had been examined for CA, 2702 for SCE and 1496 for MN. These cohorts have been followed-up with respect to subsequent cancer mortality or cancer incidence, and the expected values have been calculated from rates derived from the general populations in each country. Stratified cohort analyses will be performed with respect to the levels of the cytogenetic biomarkers. The importance of potential effect modifiers such as gender, age at test, and time since test, will be evaluated using Poisson regression models. The remaining two potential effect modifiers, occupational exposures and smoking, will be assessed in a case-referent study within the study base. 相似文献
98.
99.
Xu Q Rawlings ND Farr CL Chiu HJ Grant JC Jaroszewski L Klock HE Knuth MW Miller MD Weekes D Elsliger MA Deacon AM Godzik A Lesley SA Wilson IA 《PloS one》2011,6(7):e21875
Imelysin-like proteins define a superfamily of bacterial proteins that are likely involved in iron uptake. Members of this superfamily were previously thought to be peptidases and were included in the MEROPS family M75. We determined the first crystal structures of two remotely related, imelysin-like proteins. The Psychrobacter arcticus structure was determined at 2.15 Å resolution and contains the canonical imelysin fold, while higher resolution structures from the gut bacteria Bacteroides ovatus, in two crystal forms (at 1.25 Å and 1.44 Å resolution), have a circularly permuted topology. Both structures are highly similar to each other despite low sequence similarity and circular permutation. The all-helical structure can be divided into two similar four-helix bundle domains. The overall structure and the GxHxxE motif region differ from known HxxE metallopeptidases, suggesting that imelysin-like proteins are not peptidases. A putative functional site is located at the domain interface. We have now organized the known homologous proteins into a superfamily, which can be separated into four families. These families share a similar functional site, but each has family-specific structural and sequence features. These results indicate that imelysin-like proteins have evolved from a common ancestor, and likely have a conserved function. 相似文献
100.
Debanu Das Wang-Sik Lee Joanna C. Grant Hsiu-Ju Chiu Carol L. Farr Julie Vance Heath E. Klock Mark W. Knuth Mitchell D. Miller Marc-André Elsliger Ashley M. Deacon Adam Godzik Scott A. Lesley Stuart Kornfeld Ian A. Wilson 《The Journal of biological chemistry》2013,288(23):16789-16799
DUF2233, a domain of unknown function (DUF), is present in many bacterial and several viral proteins and was also identified in the mammalian transmembrane glycoprotein N-acetylglucosamine-1-phosphodiester α-N-acetylglucosaminidase (“uncovering enzyme” (UCE)). We report the crystal structure of BACOVA_00430, a 315-residue protein from the human gut bacterium Bacteroides ovatus that is the first structural representative of the DUF2233 protein family. A notable feature of this structure is the presence of a surface cavity that is populated by residues that are highly conserved across the entire family. The crystal structure was used to model the luminal portion of human UCE (hUCE), which is involved in targeting of lysosomal enzymes. Mutational analysis of several residues in a highly conserved surface cavity of hUCE revealed that they are essential for function. The bacterial enzyme (BACOVA_00430) has ∼1% of the catalytic activity of hUCE toward the substrate GlcNAc-P-mannose, the precursor of the Man-6-P lysosomal targeting signal. GlcNAc-1-P is a poor substrate for both enzymes. We conclude that, for at least a subset of proteins in this family, DUF2233 functions as a phosphodiester glycosidase. 相似文献