全文获取类型
收费全文 | 240篇 |
免费 | 21篇 |
出版年
2022年 | 3篇 |
2021年 | 4篇 |
2020年 | 2篇 |
2019年 | 1篇 |
2018年 | 1篇 |
2017年 | 5篇 |
2016年 | 7篇 |
2015年 | 11篇 |
2014年 | 7篇 |
2013年 | 8篇 |
2012年 | 14篇 |
2011年 | 13篇 |
2010年 | 12篇 |
2009年 | 8篇 |
2008年 | 12篇 |
2007年 | 8篇 |
2006年 | 11篇 |
2005年 | 11篇 |
2004年 | 10篇 |
2003年 | 10篇 |
2002年 | 7篇 |
2001年 | 7篇 |
2000年 | 8篇 |
1999年 | 6篇 |
1998年 | 7篇 |
1997年 | 5篇 |
1996年 | 8篇 |
1995年 | 10篇 |
1994年 | 7篇 |
1993年 | 6篇 |
1992年 | 3篇 |
1991年 | 3篇 |
1990年 | 7篇 |
1989年 | 3篇 |
1986年 | 2篇 |
1985年 | 1篇 |
1984年 | 2篇 |
1983年 | 1篇 |
1982年 | 1篇 |
1981年 | 1篇 |
1979年 | 1篇 |
1976年 | 1篇 |
1974年 | 1篇 |
1973年 | 2篇 |
1969年 | 2篇 |
1965年 | 1篇 |
排序方式: 共有261条查询结果,搜索用时 15 毫秒
81.
E M Pestili de Almeida C Piché J Sirois M Doré 《The journal of histochemistry and cytochemistry》2001,49(7):867-875
Squamous cell carcinoma is one of the most common cancers in humans and is also a frequently diagnosed neoplasm in dogs. Induction of cyclo-oxygenase-2 (COX-2), a key rate-limiting enzyme in prostaglandin biosynthesis, has been implicated in the oncogenesis of various cancers in humans, including squamous cell carcinomas. However, expression of COX-2 has not been reported in spontaneous squamous cell carcinomas of non-human species. Canine squamous cell carcinomas share several similarities with the human disease. Therefore, the objective of this study was to determine whether COX isoenzymes were expressed in naturally occurring cases of squamous cell carcinomas in dogs. Canine normal skin (n=4) and squamous cell carcinomas (n=40) were studied by immunohistochemistry and immunoblotting analysis using polyclonal antibodies selective for COX-1 or COX-2. COX-2 was strongly expressed by neoplastic keratinocytes in all cases of squamous cell carcinomas, whereas no COX-2 was detected in normal skin and in the non-neoplastic skin and oral mucosa included in the tumor tissue samples (p<0.01). Immunoblotting analysis confirmed the restricted expression of COX-2 (72,000--74,000 molecular weight doublet) in squamous cell carcinomas only. In contrast, faint COX-1 staining was found in normal skin and in squamous cell carcinomas. This study demonstrates for the first time that COX-2 is induced in canine squamous cell carcinomas, and provides a new model to investigate the role and regulation of COX-2 gene expression in naturally occurring squamous cell carcinomas. (J Histochem Cytochem 49:867-875, 2001) 相似文献
82.
Caron D Coughlan AP Simard M Bernier J Piché Y Chênevert R 《Biotechnology letters》2005,27(10):713-716
Reduction of acetophenone by Daucus carota hairy root cultures afforded (S)-phenylethanol in high yield (96%) and excellent enantiomeric excess (ee ≥ 98%). Aromatic ketones, keto esters, and a simple aliphatic ketone were reduced with good stereoselectivity (ee = 62–98%) and moderate to high chemical yields (25–90%). 相似文献
83.
Antibodies to citrullinated proteins and differences in clinical progression of rheumatoid arthritis
van der Helm-van Mil AH Verpoort KN Breedveld FC Toes RE Huizinga TW 《Arthritis research & therapy》2005,7(5):R949-R958
Antibodies to citrullinated proteins (anti-cyclic-citrullinated peptide [anti-CCP] antibodies) are highly specific for rheumatoid
arthritis (RA) and precede the onset of disease symptoms, indicating a pathogenetic role for these antibodies in RA. We recently
showed that distinct genetic risk factors are associated with either anti-CCP-positive disease or anti-CCP-negative disease.
These data are important as they indicate that distinct pathogenic mechanisms are underlying anti-CCP-positive disease or
anti-CCP-negative disease. Likewise, these observations raise the question of whether anti-CCP-positive RA and anti-CCP-negative
RA are clinically different disease entities. We therefore investigated whether RA patients with anti-CCP antibodies have
a different clinical presentation and disease course compared with patients without these autoantibodies. In a cohort of 454
incident patients with RA, 228 patients were anti-CCP-positive and 226 patients were anti-CCP-negative. The early symptoms,
tender and swollen joint count, and C-reactive protein level at inclusion, as well as the swollen joint count and radiological
destruction during 4 years of follow-up, were compared for the two groups. There were no differences in morning stiffness,
type, location and distribution of early symptoms, patients' rated disease activity and C-reactive protein at inclusion between
RA patients with and without anti-CCP antibodies. The mean tender and swollen joint count for the different joints at inclusion
was similar. At follow-up, patients with anti-CCP antibodies had more swollen joints and more severe radiological destruction.
Nevertheless, the distribution of affected joints, for swelling, bone erosions and joint space narrowing, was similar. In
conclusion, the phenotype of RA patients with or without anti-CCP antibodies is similar with respect to clinical presentation
but differs with respect to disease course. 相似文献
84.
Background
In crossbreeding programs, genomic selection offers the opportunity to make efficient use of information on crossbred (CB) individuals in the selection of purebred (PB) candidates. In such programs, reference populations often contain genotyped PB animals, although the breeding objective is usually more focused on CB performance. The question is what would be the benefit of including a larger proportion of CB individuals in the reference population.Methods
In a deterministic simulation study, we evaluated the benefit of including various proportions of CB animals in a reference population for genomic selection of PB animals in a crossbreeding program. We used a pig breeding scheme with selection for a moderately heritable trait and a size of 6000 for the reference population.Results
Applying genomic selection to improve the performance of CB individuals, with a genetic correlation between PB and CB performance (rPC) of 0.7, selection accuracy of PB candidates increased from 0.49 to 0.52 if the reference population consisted of PB individuals, it increased to 0.55 if the reference population consisted of the same number of CB individuals, and to 0.60 if the size of the CB reference population was twice that of the reference population for each PB line. The advantage of using CB rather than PB individuals increased linearly with the proportion of CB individuals in the reference population. This advantage disappeared quickly if rPC was higher or if the breeding objective put some emphasis on PB performance. The benefit of adding CB individuals to an existing PB reference population was limited for high rPC.Conclusions
Using CB rather than PB individuals in a reference population for genomic selection can provide substantial advantages, but only when correlations between PB and CB performances are not high and PB performance is not part of the breeding objective. 相似文献85.
Clarissa Dickhut Svenja Mielke Jonas Krüger Ingo Just Silke Glage Martin Meier Dirk Wedekind Andreas Pich 《Proteomics》2014,14(13-14):1674-1687
Imaging MS (MSI) has emerged as a valuable tool to study the spatial distribution of biomolecules in the brain. Herein, MALDI‐MSI was used to determine the distribution of endogenous peptides in a rat model of Usher's disease. This rare disease is considered as a leading cause of deaf‐blindness in humans worldwide. Cryosections of brain tissue were analyzed by MALDI‐MSI to differentiate between healthy and diseased rats. MSI results were highly reproducible. Tissue‐specific peptides were identified by MS/MS using LC‐Orbitrap and MALDI‐TOF/TOF analyses. These peptides were proposed for histological classification due to their particular spatial distribution in the brain, for example, substantia nigra, corpus callosum, and hippocampus. Several endogenous peptides showed significantly increased ion densities, particularly in the colliculi superiores and in the substantia nigra of diseased rats, including peptides derived from Fsd1, dystrobrevin‐β, and ProSAAS. Furthermore, several proteolytic degradation products of the myelin basic protein were identified, of which one peptide is most likely mediated by calpain‐2. Our findings contribute to the characterization of this animal model and include possible peptide markers of disease. 相似文献
86.
Gabaev I Steinbrück L Pokoyski C Pich A Stanton RJ Schwinzer R Schulz TF Jacobs R Messerle M Kay-Fedorov PC 《PLoS pathogens》2011,7(12):e1002432
Human cytomegalovirus (CMV) exerts diverse and complex effects on the immune system, not all of which have been attributed to viral genes. Acute CMV infection results in transient restrictions in T cell proliferative ability, which can impair the control of the virus and increase the risk of secondary infections in patients with weakened or immature immune systems. In a search for new immunomodulatory proteins, we investigated the UL11 protein, a member of the CMV RL11 family. This protein family is defined by the RL11 domain, which has homology to immunoglobulin domains and adenoviral immunomodulatory proteins. We show that pUL11 is expressed on the cell surface and induces intercellular interactions with leukocytes. This was demonstrated to be due to the interaction of pUL11 with the receptor tyrosine phosphatase CD45, identified by mass spectrometry analysis of pUL11-associated proteins. CD45 expression is sufficient to mediate the interaction with pUL11 and is required for pUL11 binding to T cells, indicating that pUL11 is a specific CD45 ligand. CD45 has a pivotal function regulating T cell signaling thresholds; in its absence, the Src family kinase Lck is inactive and signaling through the T cell receptor (TCR) is therefore shut off. In the presence of pUL11, several CD45-mediated functions were inhibited. The induction of tyrosine phosphorylation of multiple signaling proteins upon TCR stimulation was reduced and T cell proliferation was impaired. We therefore conclude that pUL11 has immunosuppressive properties, and that disruption of T cell function via inhibition of CD45 is a previously unknown immunomodulatory strategy of CMV. 相似文献
87.
88.
89.
Clostridium difficile causes infections ranging from mild C. difficile-associated diarrhea to severe pseudomembranous colitis. Since 2003 new hypervirulent C. difficile strains (PCR ribotype 027) emerged characterized by a dramatically increased mortality. The secretomes of the three C. difficile strains CDR20291, CD196, and CD630 were analyzed and compared. Proteins were separated and analyzed by means of SDS--PAGE and LC-MS. MS data were analyzed using Mascot and proteins were checked for export signals with SecretomeP and SignalP. LC-MS analysis revealed 158 different proteins in the supernatant of C. difficile. Most of the identified proteins originate from the cytoplasm. Thirty-two proteins in CDR20291, 36 in CD196 and 26 in CD630 were identified to be secreted by C. difficile strains. Those were mainly S-layer proteins, substrate-binding proteins of ABC-transporters, cell wall hydrolases, pilin and unknown hypothetical proteins. Toxin A and toxin B were identified after growth in brain heart infusion medium using immunological techniques. The ADP-ribosyltransferase-binding component protein, which is a part of the binary toxin CDT, was only identified in the hypervirulent ribotype 027 strains. Further proteins that are secreted specifically by hypervirulent strains were identified. 相似文献
90.
Joyce JBC van Beers Annemiek Willemze Judith Stammen-Vogelzangs Jan W Drijfhout René EM Toes Ger J M Pruijn 《Arthritis research & therapy》2012,14(1):R35-16