全文获取类型
收费全文 | 140篇 |
免费 | 32篇 |
出版年
2022年 | 1篇 |
2021年 | 1篇 |
2020年 | 1篇 |
2019年 | 2篇 |
2017年 | 1篇 |
2015年 | 10篇 |
2014年 | 11篇 |
2013年 | 9篇 |
2012年 | 5篇 |
2011年 | 10篇 |
2010年 | 4篇 |
2009年 | 3篇 |
2008年 | 11篇 |
2007年 | 8篇 |
2006年 | 5篇 |
2005年 | 8篇 |
2004年 | 13篇 |
2003年 | 9篇 |
2002年 | 3篇 |
2001年 | 3篇 |
2000年 | 7篇 |
1999年 | 3篇 |
1998年 | 2篇 |
1997年 | 1篇 |
1996年 | 4篇 |
1995年 | 7篇 |
1994年 | 3篇 |
1992年 | 3篇 |
1991年 | 3篇 |
1990年 | 2篇 |
1989年 | 3篇 |
1988年 | 5篇 |
1987年 | 1篇 |
1984年 | 1篇 |
1983年 | 2篇 |
1980年 | 1篇 |
1975年 | 2篇 |
1970年 | 1篇 |
1966年 | 1篇 |
1953年 | 1篇 |
1947年 | 1篇 |
排序方式: 共有172条查询结果,搜索用时 15 毫秒
51.
52.
Jason R. Buck Eliot T. McKinley Allie Fu Ty W. Abel Reid C. Thompson Lola Chambless Jennifer M. Watchmaker James P. Harty Michael K. Cooper H. Charles Manning 《PloS one》2015,10(10)
Current positron emission tomography (PET) imaging biomarkers for detection of infiltrating gliomas are limited. Translocator protein (TSPO) is a novel and promising biomarker for glioma PET imaging. To validate TSPO as a potential target for molecular imaging of glioma, TSPO expression was assayed in a tumor microarray containing 37 high-grade (III, IV) gliomas. TSPO staining was detected in all tumor specimens. Subsequently, PET imaging was performed with an aryloxyanilide-based TSPO ligand, [18F]PBR06, in primary orthotopic xenograft models of WHO grade III and IV gliomas. Selective uptake of [18F]PBR06 in engrafted tumor was measured. Furthermore, PET imaging with [18F]PBR06 demonstrated infiltrative glioma growth that was undetectable by traditional magnetic resonance imaging (MRI). Preliminary PET with [18F]PBR06 demonstrated a preferential tumor-to-normal background ratio in comparison to 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG). These results suggest that TSPO PET imaging with such high-affinity radiotracers may represent a novel strategy to characterize distinct molecular features of glioma growth, as well as better define the extent of glioma infiltration for therapeutic purposes. 相似文献
53.
54.
Anthony H Taylor Mark Finney Patricia MW Lam Justin C Konje 《Reproductive biology and endocrinology : RB&E》2011,9(1):1-18
Background
In early pregnancy, increased plasma levels of the endocannabinoid anandamide (AEA) are associated with miscarriage through mechanisms that might affect the developing placenta or maternal decidua.Methods
In this study, we compare AEA levels in failed and viable pregnancies with the levels of the trophoblastic hormones (beta-human chorionic gonadotrophin (beta-hCG), progesterone (P4) and (pregnancy-associated placental protein-A (PAPP-A)) essential for early pregnancy success and relate that to the expression of the cannabinoid receptors and enzymes that modulate AEA levels.Results
The median plasma AEA level in non-viable pregnancies (1.48 nM; n = 20) was higher than in viable pregnancies (1.21 nM; n = 25; P = 0.013), as were progesterone and beta-hCG levels (41.0 vs 51.5 ng/mL; P = 0.052 for P4 and 28,650 vs 6,560 mIU/L; P = 0.144 for beta-hCG, respectively, but were not statistically significant). Serum PAPP-A levels in the viable group were approximately 6.8 times lower than those in the non-viable group (1.82 vs 12.25 mg/L; P = 0.071), but again these differences were statistically insignificant. In the spontaneous miscarriage group, significant correlations between P4 and beta-hCG, P4 and PAPP-A and AEA and PAPP-A levels were observed. Simultaneously, immunohistochemical distributions of the two main cannabinoid receptors and the AEA-modifying enzymes, fatty acid amide hydrolase (FAAH) and N-acylphosphatidylethanolamine-phospholipase D (NAPE-PLD), changed within both the decidua and trophoblast.Conclusions
The association of higher AEA levels with early pregnancy failure and with beta-hCG and PAPP-A, but not with progesterone concentrations suggest that plasma AEA levels and pregnancy failure are linked via a mechanism that may involve trophoblastic beta-hCG, and PAPP-A, but not, progesterone production. Although the trophoblast, decidua and embryo contain receptors for AEA, the main AEA target in early pregnancy failure remains unknown. 相似文献55.
van de Geijn FE de Man YA Wuhrer M Willemsen SP Deelder AM Hazes JM Dolhain RJ 《Arthritis research & therapy》2011,13(1):R10
Introduction
Rheumatoid arthritis (RA) improves during pregnancy and flares after delivery. It has been hypothesized that high levels of the complement factor mannose-binding lectin (MBL) are associated with a favourable disease course of RA by facilitating the clearance of pathogenic immunoglobulin G (IgG) lacking galactose sugar moieties. During pregnancy, increased galactosylation of IgG and simultaneously increased MBL levels can be observed, with the latter being strictly related to maternal MBL genotypes. Therefore, increased MBL levels in concert with increased IgG galactosylation may be associated with pregnancy-induced improvement of RA. The objective of this study was to investigate whether MBL genotypes are associated with changes in RA disease activity and with changes in IgG galactosylation during pregnancy and in the postpartum period. We also studied the association between MBL genotypes and pregnancy outcomes in RA. 相似文献56.
57.
T-helper 17 cell cytokines and interferon type I: partners in crime in systemic lupus erythematosus?
Zana Brkic Odilia BJ Corneth Cornelia G van Helden-Meeuwsen Radboud JEM Dolhain Naomi I Maria Sandra MJ Paulissen Nadine Davelaar Jan Piet van Hamburg Paul L van Daele Virgil A Dalm P Martin van Hagen Johanna MW Hazes Marjan A Versnel Erik Lubberts 《Arthritis research & therapy》2014,16(2):R62
Introduction
A hallmark of systemic autoimmune diseases like systemic lupus erythematosus (SLE) is the increased expression of interferon (IFN) type I inducible genes, so-called IFN type I signature. Recently, T-helper 17 subset (Th17 cells), which produces IL-17A, IL-17F, IL-21, and IL-22, has been implicated in SLE. As CCR6 enriches for Th17 cells, we used this approach to investigate whether CCR6+ memory T-helper cells producing IL-17A, IL-17F, IL-21, and/or IL-22 are increased in SLE patients and whether this increase is related to the presence of IFN type I signature.Methods
In total, 25 SLE patients and 15 healthy controls (HCs) were included. SLE patients were divided into IFN type I signature-positive (IFN+) (n = 16) and negative (IFN-) (n = 9) patients, as assessed by mRNA expression of IFN-inducible genes (IFIGs) in monocytes. Expression of IL-17A, IL-17F, IL-21, and IL-22 by CD4+CD45RO+CCR6+ T cells (CCR6+ cells) was measured with flow cytometry and compared between IFN+, IFN- patients and HCs.Results
Increased percentages of IL-17A and IL-17A/IL-17F double-producing CCR6+ cells were observed in IFN+ patients compared with IFN- patients and HCs. IL-17A and IL-17F expression within CCR6+ cells correlated significantly with IFIG expression. In addition, we found significant correlation between B-cell activating factor of the tumor necrosis family (BAFF)–a factor strongly correlating with IFN type I - and IL-21 producing CCR6+ cells.Conclusions
We show for the first time higher percentages of IL-17A and IL-17A/IL-17F double-producing CCR6+ memory T-helper cells in IFN+ SLE patients, supporting the hypothesis that IFN type I co-acts with Th17 cytokines in SLE pathogenesis. 相似文献58.
59.
Haring JS Jing X Bollenbacher-Reilley J Xue HH Leonard WJ Harty JT 《Journal of immunology (Baltimore, Md. : 1950)》2008,180(5):2855-2862
Expression of IL-7Ralpha (CD127) has been suggested as a major determinant in the survival of memory T cell precursors. We investigated whether constitutive expression of IL-7Ralpha on T cells increased expansion and/or decreased contraction of endogenous Ag-specific CD4 and CD8 T cells following infection with Listeria monocytogenes. The results indicate that constitutive expression of IL-7Ralpha alone was not enough to impart an expansion or survival advantage to CD8 T cells responding to infection, and did not increase memory CD8 T cell numbers over those observed in wild-type controls. Constitutive expression of IL-7Ralpha did allow for slightly prolonged expansion of Ag-specific CD4 T cells; however, it did not alter the contraction phase or protect against the waning of memory T cell numbers at later times after infection. Memory CD4 and CD8 T cells generated in IL-7Ralpha transgenic mice expanded similarly to wild-type T cells after secondary infection, and immunized IL-7Ralpha transgenic mice were fully protected against lethal bacterial challenge demonstrating that constitutive expression of IL-7Ralpha does not impair, or markedly improve memory/secondary effector T cell function. These results indicate that expression of IL-7Ralpha alone does not support increased survival of effector Ag-specific CD4 or CD8 T cells into the memory phase following bacterial infection. 相似文献
60.
Langley DB Harty DW Jacques NA Hunter N Guss JM Collyer CA 《Journal of molecular biology》2008,377(1):104-116
The crystal structure of GcnA, an N-acetyl-β-d-glucosaminidase from Streptococcus gordonii, was solved by multiple wavelength anomalous dispersion phasing using crystals of selenomethionine-substituted protein. GcnA is a homodimer with subunits each comprised of three domains. The structure of the C-terminal α-helical domain has not been observed previously and forms a large dimerisation interface. The fold of the N-terminal domain is observed in all structurally related glycosidases although its function is unknown. The central domain has a canonical (β/α)8 TIM-barrel fold which harbours the active site. The primary sequence and structure of this central domain identifies the enzyme as a family 20 glycosidase. Key residues implicated in catalysis have different conformations in two different crystal forms, which probably represent active and inactive conformations of the enzyme. The catalytic mechanism for this class of glycoside hydrolase, where the substrate rather than the enzyme provides the cleavage-inducing nucleophile, has been confirmed by the structure of GcnA complexed with a putative reaction intermediate analogue, N-acetyl-β-d-glucosamine-thiazoline. The catalytic mechanism is discussed in light of these and other family 20 structures. 相似文献