全文获取类型
收费全文 | 198篇 |
免费 | 17篇 |
出版年
2022年 | 1篇 |
2021年 | 3篇 |
2020年 | 3篇 |
2019年 | 2篇 |
2018年 | 2篇 |
2017年 | 4篇 |
2016年 | 8篇 |
2015年 | 11篇 |
2014年 | 15篇 |
2013年 | 13篇 |
2012年 | 21篇 |
2011年 | 25篇 |
2010年 | 16篇 |
2009年 | 7篇 |
2008年 | 14篇 |
2007年 | 15篇 |
2006年 | 11篇 |
2005年 | 8篇 |
2004年 | 10篇 |
2003年 | 2篇 |
2002年 | 4篇 |
2001年 | 1篇 |
2000年 | 1篇 |
1999年 | 3篇 |
1998年 | 5篇 |
1997年 | 1篇 |
1993年 | 2篇 |
1990年 | 1篇 |
1988年 | 1篇 |
1983年 | 1篇 |
1979年 | 1篇 |
1978年 | 1篇 |
1971年 | 1篇 |
1967年 | 1篇 |
排序方式: 共有215条查询结果,搜索用时 109 毫秒
181.
Annemieke Schuurhof Riny Janssen Hanneke de Groot Hennie M Hodemaekers Arja de Klerk Jan LL Kimpen Louis Bont 《Respiratory research》2011,12(1):121
Background
Respiratory syncytial virus (RSV) is the most common cause of bronchiolitis in infants. Following RSV bronchiolitis, 50% of children develop post-bronchiolitis wheeze (PBW). Animal studies have suggested that interleukin (IL)-10 plays a critical role in the pathogenesis of RSV bronchiolitis and subsequent airway hyperresponsiveness. Previously, we showed that ex vivo monocyte IL-10 production is a predictor of PBW. Additionally, heterozygosity of the single-nucleotide polymorphism (SNP) rs1800872 in the IL10 promoter region was associated with protection against RSV bronchiolitis.Methods
This study aimed to determine the in vivo role of IL-10 in RSV pathogenesis and recurrent wheeze in a new cohort of 235 infants hospitalized for RSV bronchiolitis. IL-10 levels in nasopharyngeal aspirates (NPAs) were measured at the time of hospitalization and the IL10 SNP rs1800872 genotype was determined. Follow-up data were available for 185 children (79%).Results
Local IL-10 levels during RSV infection turned out to be higher in infants that later developed physician diagnosed PBW as compared to infants without PBW in the first year after RSV infection (958 vs 692 pg/ml, p = 0.02). The IL10 promoter SNP rs1800872 was not associated with IL-10 concentration in NPAs.Conclusion
The relationship between high local IL-10 levels during the initial RSV infection and physician diagnosed PBW provides further evidence of the importance of the IL-10 response during RSV bronchiolitis. 相似文献182.
At the early onset of the 20th century, several studies already reported that the gray matter was implicated in the histopathology of multiple sclerosis
(MS). However, as white matter pathology long received predominant attention in this disease, and histological staining techniques
for detecting myelin in the gray matter were suboptimal, it was not until the beginning of the 21st century that the true extent and importance of gray matter pathology in MS was finally recognized. Gray matter damage was
shown to be frequent and extensive, and more pronounced in the progressive disease phases. Several studies subsequently demonstrated
that the histopathology of gray matter lesions differs from that of white matter lesions. Unfortunately, imaging of pathology
in gray matter structures proved to be difficult, especially when using conventional magnetic resonance imaging (MRI) techniques.
However, with the recent introduction of several more advanced MRI techniques, the detection of cortical and subcortical damage
in MS has considerably improved. This has important consequences for studying the clinical correlates of gray matter damage.
In this review, we provide an overview of what has been learned about imaging of gray matter damage in MS, and offer a brief
perspective with regards to future developments in this field. 相似文献
183.
Nikolova M Carriere M Jenabian MA Limou S Younas M Kök A Huë S Seddiki N Hulin A Delaneau O Schuitemaker H Herbeck JT Mullins JI Muhtarova M Bensussan A Zagury JF Lelievre JD Lévy Y 《PLoS pathogens》2011,7(7):e1002110
HIV-1 infection is characterized by a chronic activation of the immune system and suppressed function of T lymphocytes. Regulatory CD4+ CD25(high) FoxP3+CD127(low) T cells (Treg) play a key role in both conditions. Here, we show that HIV-1 positive patients have a significant increase of Treg-associated expression of CD39/ENTPD1, an ectoenzyme which in concert with CD73 generates adenosine. We show in vitro that the CD39/adenosine axis is involved in Treg suppression in HIV infection. Treg inhibitory effects are relieved by CD39 down modulation and are reproduced by an adenosine-agonist in accordance with a higher expression of the adenosine A2A receptor on patients' T cells. Notably, the expansion of the Treg CD39+ correlates with the level of immune activation and lower CD4+ counts in HIV-1 infected patients. Finally, in a genetic association study performed in three different cohorts, we identified a CD39 gene polymorphism that was associated with down-modulated CD39 expression and a slower progression to AIDS. 相似文献
184.
185.
Moser J Volker M Kool H Alekseev S Vrieling H Yasui A van Zeeland AA Mullenders LH 《DNA Repair》2005,4(5):571-582
Previous studies point to the XPC-hHR23B complex as the principal initiator of global genome nucleotide excision repair (NER) pathway, responsible for the repair of UV-induced cyclobutane pyrimidine dimers (CPD) and 6-4 photoproducts (6-4PP) in human cells. However, the UV-damaged DNA binding protein (UV-DDB) has also been proposed as a damage recognition factor involved in repair of UV-photoproducts, especially CPD. Here, we show in human XP-E cells (UV-DDB deficient) that the incision complex formation at UV-induced lesions was severely diminished in locally damaged nuclear spots. Repair kinetics of CPD and 6-4PP in locally and globally UV-irradiated normal human and XP-E cells demonstrate that UV-DDB can mediate efficient targeting of XPC-hHR23B and other NER factors to 6-4PP. The data is consistent with a mechanism in which UV-DDB forms a stable complex when bound to a 6-4PP, allowing subsequent repair proteins--starting with XPC-hHR23B--to accumulate, and verify the lesion, resulting in efficient 6-4PP repair. These findings suggest that (i) UV-DDB accelerates repair of 6-4PP, and at later time points also CPD, (ii) the fraction of 6-4PP that can be bound by UV-DDB is limited due to its low cellular quantity and fast UV dependent degradation, and (iii) in the absence of UV-DDB a slow XPC-hHR23B dependent pathway is capable to repair 6-4PP, and to some extent also CPD. 相似文献
186.
Low immune activation despite high levels of pathogenic human immunodeficiency virus type 1 results in long-term asymptomatic disease 总被引:3,自引:1,他引:2
下载免费PDF全文
![点击此处可从《Journal of virology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Choudhary SK Vrisekoop N Jansen CA Otto SA Schuitemaker H Miedema F Camerini D 《Journal of virology》2007,81(16):8838-8842
Long-term asymptomatic human immunodeficiency virus (HIV)-infected individuals (LTA) usually have low viral load and low immune activation. To discern whether viral load or immune activation is dominant in determining progression to AIDS, we studied three exceptional LTA with high viral loads. HIV type 1 isolates from these LTA were as pathogenic as viruses from progressors in organ culture. Despite high viral loads, these LTA had low levels of proliferating and activated T cells compared to progressors, like other LTA. In contrast to those in progressors, HIV-specific CD4(+) T-cell responses in these LTA were maintained. Thus, low immune activation despite a high viral load preserved HIV-specific T-cell responses and resulted in a long-term asymptomatic phenotype. 相似文献
187.
Laura E. McCoy Emilia Falkowska Katie J. Doores Khoa Le Devin Sok Marit J. van Gils Zelda Euler Judith A. Burger Michael S. Seaman Rogier W. Sanders Hanneke Schuitemaker Pascal Poignard Terri Wrin Dennis R. Burton 《PLoS pathogens》2015,11(8)
The broadly neutralizing HIV monoclonal antibodies (bnMAbs) PG9, PG16, PGT151, and PGT152 have been shown earlier to occasionally display an unusual virus neutralization profile with a non-sigmoidal slope and a plateau at <100% neutralization. In the current study, we were interested in determining the extent of non-sigmoidal slopes and plateaus at <100% for HIV bnMAbs more generally. Using both a 278 panel of pseudoviruses in a CD4 T-cell (U87.CCR5.CXCR4) assay and a panel of 117 viruses in the TZM-bl assay, we found that bnMAbs targeting many neutralizing epitopes of the spike had neutralization profiles for at least one virus that plateaued at <90%. Across both panels the bnMAbs targeting the V2 apex of Env and gp41 were most likely to show neutralization curves that plateaued <100%. Conversely, bnMAbs targeting the high-mannose patch epitopes were less likely to show such behavior. Two CD4 binding site (CD4bs) Abs also showed this behavior relatively infrequently. The phenomenon of incomplete neutralization was also observed in a large peripheral blood mononuclear cells (PBMC)-grown molecular virus clone panel derived from patient viral swarms. In addition, five bnMAbs were compared against an 18-virus panel of molecular clones produced in 293T cells and PBMCs and assayed in TZM-bl cells. Examples of plateaus <90% were seen with both types of virus production with no consistent patterns observed. In conclusion, incomplete neutralization and non-sigmoidal neutralization curves are possible for all HIV bnMAbs against a wide range of viruses produced and assayed in both cell lines and primary cells with implications for the use of antibodies in therapy and as tools for vaccine design. 相似文献
188.
Linda Heijmen Edwin E. G. W. ter Voert Wim J. G. Oyen Cornelis J. A. Punt Dick Johan van Spronsen Arend Heerschap Lioe-Fee de Geus-Oei Hanneke W. M. van Laarhoven 《PloS one》2015,10(4)
Aim
Aim of this study was to investigate the potential of 18F-FDG PET, diffusion weighted imaging (DWI) and susceptibility-weighted (T2*) MRI to predict response to systemic treatment in patients with colorectal liver metastases. The predictive values of pretreatment measurements and of early changes one week after start of therapy, were evaluated.Methods
Imaging was performed prior to and one week after start of first line chemotherapy in 39 patients with colorectal liver metastases. 18F-FDG PET scans were performed on a PET/CT scanner and DWI and T2* were performed on a 1.5T MR scanner. The maximum standardized uptake values (SUV), total lesion glycolysis (TLG), apparent diffusion coefficient (ADC) and T2* value were assessed in the same lesions. Up to 5 liver metastases per patient were analyzed. Outcome measures were progression free survival (PFS), overall survival (OS) and size response.Results
Pretreatment, high SUVmax, high TLG, low ADC and high T2* were associated with a shorter OS. Low pretreatment ADC value was associated with shorter PFS. After 1 week a significant drop in SUVmax and rise in ADC were observed. The drop in SUV was correlated with the rise in ADC (r=-0.58, p=0.002). Neither change in ADC nor in SUV was predictive of PFS or OS. T2* did not significantly change after start of treatment.Conclusion
Pretreatment SUVmax, TLG, ADC, and T2* values in colorectal liver metastases are predictive of patient outcome. Despite sensitivity of DWI and 18F-FDG PET for early treatment effects, change in these parameters was not predictive of long term outcome. 相似文献189.
190.
QTL analysis to study the association between leaf size and abscisic acid accumulation in droughted rice leaves and comparisons across cereals 总被引:5,自引:0,他引:5
Quarrie Stephen A. Laurie David A. Zhu Jiahui Lebreton Claude Semikhodskii Andrei Steed Andrew Witsenboer Hanneke Calestani Christina 《Plant molecular biology》1997,35(1-2):155-165
Plants accumulate abscisic acid (ABA) under droughted conditions. Genetic variation in the accumulation of ABA in detached and partially dehydrated leaves of rice has previously been reported, and this was found to be associated with variation in leaf size (smaller leaves made more ABA). Correlation analysis failed to distinguish clearly between a causal relationship between the two traits and close genetic linkage between loci controlling the traits. Here we present a detailed genetic analysis of ABA accumulation in detached and partially dehydrated rice leaves, using a population of F2 plants generated from the lowland × upland cross IR20 (high-ABA) × 63-83 (low-ABA) which was mapped with RFLP and AFLP markers. Several highly significant quantitative trait loci (QTLs) for ABA accumulation and leaf weight were identified. Only one of the minor QTLs for ABA accumulation (accounting for only 4% of the phenotypic variance) was coincident with any QTLs for leaf size such that the high-ABA allele was associated with smaller leaves. This analysis, therefore, showed that the association previously found between ABA accumulation and leaf size was probably largely due to genetic linkage and not to a direct effect of leaf size on ABA accumulation or vice versa. Because of the importance of ABA accumulation in regulating responses of plants to drought stress and the effects of plant size on the rate of development of stress, QTLs for drought-induced ABA accumulation, leaf size and tiller number were compared between rice and wheat. In particular, a possible location in rice was sought for a homoeologue of the major wheat vernalization responsive gene, Vrn1, as this gene is also associated with major effects on leaf size, tiller number and ABA accumulation in wheat. The likelihood of homoeologous loci regulating ABA accumulation, leaf size and tiller number in the two crops is discussed. 相似文献