首页 | 本学科首页   官方微博 | 高级检索  
文章检索
  按 检索   检索词:      
出版年份:   被引次数:   他引次数: 提示:输入*表示无穷大
  收费全文   294篇
  免费   17篇
  2023年   2篇
  2022年   2篇
  2021年   4篇
  2020年   3篇
  2019年   9篇
  2018年   5篇
  2017年   6篇
  2016年   7篇
  2015年   16篇
  2014年   15篇
  2013年   14篇
  2012年   26篇
  2011年   21篇
  2010年   18篇
  2009年   23篇
  2008年   22篇
  2007年   22篇
  2006年   16篇
  2005年   20篇
  2004年   13篇
  2003年   16篇
  2002年   15篇
  2000年   1篇
  1999年   1篇
  1998年   1篇
  1997年   1篇
  1996年   4篇
  1995年   1篇
  1994年   1篇
  1993年   2篇
  1992年   1篇
  1981年   1篇
  1978年   2篇
排序方式: 共有311条查询结果,搜索用时 15 毫秒
1.
The protein encoded by ORF9 is essential for varicella-zoster virus (VZV) replication. Previous studies documented its presence in the trans-Golgi network and its involvement in secondary envelopment. In this work, we deleted the ORF9p acidic cluster, destroying its interaction with ORF47p, and this resulted in a nuclear accumulation of both proteins. This phenotype results in an accumulation of primary enveloped capsids in the perinuclear space, reflecting a capsid de-envelopment defect.  相似文献   
2.

Purpose

The hyperdense basilar artery sign (HBAS) is an indicator of vessel occlusion on non contrast-enhanced computer tomography (NECT) in acute stroke patients. Since basilar artery occlusion (BAO) is associated with a high mortality and morbidity, its early detection is of great clinical value. We sought to analyze the influence of density measurement as well as a normalized ratio of Hounsfield unit/hematocrit (HU/Hct) ratio on the detection of BAO on NECT in patients with suspected BAO.

Materials and Methods

102 patients with clinically suspected BAO were examined with NECT followed immediately by Multidetector computed tomography Angiography. Two observers independently analyzed the images regarding the presence or absence of HBAS on NECT and performed HU measurements in the basilar artery. Receiver operating characteristic curve analysis was performed to determine the optimal density threshold for BAO using attenuation measurements or HU/Hct ratio.

Results

Sensitivity of visual detection of the HBAS on NECT was relatively low 81% (95%-CI, 54–95%) while specificity was high 91% (95%-CI, 82–96%). The highest sensitivity was achieved by the combination of visual assessment and additional quantitative attenuation measurements applying a cut-off value of 46.5 HU with 94% sensitivity and 81% specificity for BAO. A HU/Hct ratio >1.32 revealed sensitivity of 88% (95%-CI, 60–98%) and specificity of 84% (95%-CI, 74–90%).

Conclusion

In patients with clinically suspected acute BAO the combination of visual assessment and additional attenuation measurement with a cut-off value of 46.5 HU is a reliable approach with high sensitivity in the detection of BAO on NECT.  相似文献   
3.
Patients with Disorders of Sex Development (DSD), especially those with gonadal dysgenesis and hypovirilization are at risk of developing malignant type II germ cell tumors/cancer (GCC) (seminoma/dysgerminoma and nonseminoma), with either carcinoma in situ (CIS) or gonadoblastoma (GB) as precursor lesion. In 10-15% of 46,XY gonadal dysgenesis cases (i.e., Swyer syndrome), SRY mutations, residing in the HMG (High Mobility Group) domain, are found to affect nuclear transport or binding to and bending of DNA. Frasier syndrome (FS) is characterized by gonadal dysgenesis with a high risk for development of GB as well as chronic renal failure in early adulthood, and is known to arise from a splice site mutation in intron 9 of the Wilms' tumor 1 gene (WT1). Mutations in SRY as well as WT1 can lead to diminished expression and function of SRY, resulting in sub-optimal SOX9 expression, Sertoli cell formation and subsequent lack of proper testicular development. Embryonic germ cells residing in this unfavourable micro-environment have an increased risk for malignant transformation. Here a unique case of a phenotypically normal female (age 22 years) is reported, presenting with primary amenorrhoea, later diagnosed as hypergonadotropic hypogonadism on the basis of 46,XY gonadal dygenesis with a novel missense mutation in SRY. Functional in vitro studies showed no convincing protein malfunctioning. Laparoscopic examination revealed streak ovaries and a normal, but small, uterus. Pathological examination demonstrated bilateral GB and dysgerminoma, confirmed by immunohistochemistry. Occurrence of a delayed progressive kidney failure (focal segmental glomerular sclerosis) triggered analysis of WT1, revealing a pathogenic splice-site mutation in intron 9. Analysis of the SRY gene in an additional five FS cases did not reveal any mutations. The case presented shows the importance of multi-gene based diagnosis of DSD patients, allowing early diagnosis and treatment, thus preventing putative development of an invasive cancer.  相似文献   
4.
The mannose 6-phosphate (Man-6-P) lysosomal targeting signal on acid hydrolases is synthesized by the sequential action of uridine 5′-diphosphate-N-acetylglucosamine: lysosomal enzyme N-acetylglucosamine-1-phosphotransferase (GlcNAc-1-phosphotransferase) and GlcNAc-1-phosphodiester α-N-acetylglucosaminidase (“uncovering enzyme” or UCE). Mutations in the two genes that encode GlcNAc-1-phosphotransferase give rise to lysosomal storage diseases (mucolipidosis type II and III), whereas no pathological conditions have been associated with the loss of UCE activity. To analyze the consequences of UCE deficiency, the UCE gene was inactivated via insertional mutagenesis in mice. The UCE −/− mice were viable, grew normally and lacked detectable histologic abnormalities. However, the plasma levels of six acid hydrolases were elevated 1.6- to 5.4-fold over wild-type levels. These values underestimate the degree of hydrolase hypersecretion as these enzymes were rapidly cleared from the plasma by the mannose receptor. The secreted hydrolases contained GlcNAc-P-Man diesters, exhibited a decreased affinity for the cation-independent mannose 6-phosphate receptor and failed to bind to the cation-dependent mannose 6-phosphate receptor. These data demonstrate that UCE accounts for all the uncovering activity in the Golgi. We propose that in the absence of UCE, the weak binding of the acid hydrolases to the cation-independent mannose 6-phosphate receptor allows sufficient sorting to lysosomes to prevent the tissue abnormalities seen with GlcNAc-1-phosphotranferase deficiency.  相似文献   
5.
A growing body of evidence suggests that interactions between pollen grains and environmental pollutants, especially air pollutants, could be of critical importance with regard to the increase in allergic responses observed in the past decades. Using birch pollen grains (BPG), a major allergy source in European countries, and lead (Pb), a highly toxic metal trace element (MTE) present in urban areas, the immune response of human epithelial cells exposed to BPG or to Pb-associated BPG was compared. The cellular response after exposure either to BPG, BPG exposed to 30?mg/L of Pb (BPG-30), or BPG exposed to 60?mg/L of Pb (BPG-60) was evaluated after two time lapses (2 and 6?h) by measuring mRNA levels of four mediators, including two inflammatory (interleukin-8 and interleukin-6) and two allergic (interleukin-5 [IL-5] and interleukin-13) cytokines. After 2?h of exposure, significant upregulation of the IL-5 gene was observed after exposure to BPG-60 in comparison with exposure to BPG and BPG-30 (N IL-5?=?1.9, Mann?CWhitney test, p?=?0.003). After 6?h of exposure, significant upregulation of the IL-5 gene was observed after exposure to BPG-30 with N IL-5?=?1.8 and to BPG-60 with N IL-5?=?2.3 (Mann?CWhitney test, p?=?0.0029) in comparison with exposure to BPG. This first attempt to investigate the influence of pollution by MTE on pollen grain showed a dose?Ctime-dependent increase in IL-5 gene expression after exposure to BPG combined to Pb.  相似文献   
6.
7.
8.
The entry of retroviruses into cells depends on receptor recognition by the viral envelope surface subunit SU followed by membrane fusion, which is thought to be mediated by a fusion peptide located at the amino terminus of the envelope transmembrane subunit TM. Several fusion determinants have been previously identified in murine leukemia virus (MLV) envelopes, but their functional interrelationships as well as the processes involved in fusion activation upon retroviral receptor recognition remain unelucidated. Despite both structural and functional similarities of their envelope glycoproteins, ecotropic and amphotropic MLVs display two different postbinding properties: (i) while amphotropic MLVs fuse the cells at neutral pH, penetration of ecotropic MLVs is relatively acid pH dependent and (ii) ecotropic envelopes are more efficient than amphotropic envelopes in inducing cell-to-cell fusion and syncytium formation. By exploiting the latter characteristic in the analysis of chimeras of ecotropic and amphotropic MLV envelopes, we show here that substitution of the ecotropic MLV proline-rich region (PRR), located in the SU between the amino-terminal receptor binding domain and the TM-interacting SU carboxy-terminal domains, is sufficient to revert the amphotropic low-fusogenic phenotype into a high-fusogenic one. Furthermore, we have identified potential β-turns in the PRR that control the stability of SU-TM associations as well as the thresholds required to trigger either cell-to-cell or virus-to-cell fusion. These data, demonstrating that the PRR functions as a signal which induces envelope conformational changes leading to fusion, have enabled us to derive envelopes which can infect cells harboring low levels of available amphotropic receptors.  相似文献   
9.
10.
Plant phenology—the timing of cyclic or recurrent biological events in plants—offers insight into the ecology, evolution, and seasonality of plant‐mediated ecosystem processes. Traditionally studied phenologies are readily apparent, such as flowering events, germination timing, and season‐initiating budbreak. However, a broad range of phenologies that are fundamental to the ecology and evolution of plants, and to global biogeochemical cycles and climate change predictions, have been neglected because they are “cryptic”—that is, hidden from view (e.g., root production) or difficult to distinguish and interpret based on common measurements at typical scales of examination (e.g., leaf turnover in evergreen forests). We illustrate how capturing cryptic phenology can advance scientific understanding with two case studies: wood phenology in a deciduous forest of the northeastern USA and leaf phenology in tropical evergreen forests of Amazonia. Drawing on these case studies and other literature, we argue that conceptualizing and characterizing cryptic plant phenology is needed for understanding and accurate prediction at many scales from organisms to ecosystems. We recommend avenues of empirical and modeling research to accelerate discovery of cryptic phenological patterns, to understand their causes and consequences, and to represent these processes in terrestrial biosphere models.  相似文献   
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号