全文获取类型
收费全文 | 107篇 |
免费 | 6篇 |
出版年
2023年 | 1篇 |
2022年 | 2篇 |
2021年 | 9篇 |
2020年 | 1篇 |
2019年 | 2篇 |
2018年 | 2篇 |
2017年 | 1篇 |
2016年 | 2篇 |
2015年 | 3篇 |
2014年 | 9篇 |
2013年 | 8篇 |
2012年 | 12篇 |
2011年 | 7篇 |
2010年 | 3篇 |
2009年 | 4篇 |
2008年 | 11篇 |
2007年 | 1篇 |
2006年 | 8篇 |
2005年 | 2篇 |
2004年 | 6篇 |
2003年 | 2篇 |
2002年 | 7篇 |
2001年 | 2篇 |
1997年 | 1篇 |
1996年 | 1篇 |
1995年 | 1篇 |
1989年 | 1篇 |
1988年 | 1篇 |
1982年 | 1篇 |
1979年 | 1篇 |
1970年 | 1篇 |
排序方式: 共有113条查询结果,搜索用时 15 毫秒
1.
2.
Skeletal or cardiac muscle fibers can be separated by brief (3-5 second) dissociation of formalin-fixed pieces with a Willems Polytron (Brinkmann Instrument Co.). Such separated fibers are useful for demonstration of abnormal accumulations of lipids, carbohydrates, proteins and minerals in metabolic diseases. Staining techniques for demonstration of various stored materials include: 1) toluidine blue at pH 2.8 for acid mucopolysaccharide in skeletal muscle fibers in Pompe's glycogenesis 2,2) one-step trichrome stain for nemaline myopathy and for abnormal mitochondria in X-linked infantile cardiomyopathy, 3) periodic acid-methenamine silver stain for glycolipid-containing lysosomes in I-cell disease (mucolipidosis 2), 4) Sudan black B stain for lipid in skeletal muscle fibers in Reye's syndrome, infantile lactic acidosis, Leigh's infantile subacute necrotizing encephalopathy and Jansky-Bielschowsky late infantile ceroid lipofuscinosis, 5) iron stain for iron in cardiac and skeletal muscle fibers in thalassemia with advanced hemosiderosis, and 6) autofluorescence for “ceroid” in skeletal muscle fibers in Jansky-Bielschowsky disease. 相似文献
3.
Lianne Koens Yongjun Qin Wai Y. Leung Willem E. Corver Patty M. Jansen Rein Willemze Maarten H. Vermeer Cornelis P. Tensen 《PloS one》2013,8(12)
Aberrant expression of microRNAs is widely accepted to be pathogenetically involved in nodal diffuse large B-cell lymphomas (DLBCLs). However, the microRNAs profiles of primary cutaneous large B-cell lymphomas (PCLBCLs) are not yet described. Its two main subtypes, i.e., primary cutaneous diffuse large B-cell lymphoma, leg type (PCLBCL-LT) and primary cutaneous follicle center lymphoma (PCFCL) are characterized by an activated B-cell (ABC)-genotype and a germinal center B-cell (GCB)-genotype, respectively. We performed high-throughput sequencing analysis on frozen tumor biopsies from 19 cases of PCFCL and PCLBCL-LT to establish microRNA profiles. Cluster analysis of the complete microRNome could not distinguish between the two subtypes, but 16 single microRNAs were found to be differentially expressed. Single microRNA RT-qPCR was conducted on formalin-fixed paraffin-embedded tumor biopsies of 20 additional cases, confirming higher expression of miR-9-5p, miR-31-5p, miR-129-2-3p and miR-214-3p in PCFCL as compared to PCLBCL-LT. MicroRNAs previously described to be higher expressed in ABC-type as compared to GCB-type nodal DLBCL were not differentially expressed between PCFCL and PCLBCL-LT. In conclusion, PCFCL and PCLBCL-LT differ in their microRNA profiles. In contrast to their gene expression profile, they only show slight resemblance with the microRNA profiles found in GCB- and ABC-type nodal DLBCL. 相似文献
4.
K. Kraaier A. H. Starrenburg R. M. Verheggen J. van der Palen M. F. Scholten 《Netherlands heart journal》2013,21(4):191-195
Background
Implantable cardioverter defibrillators (ICDs) are designed to deliver shocks or antitachycardia pacing (ATP) in the event of ventricular arrhythmias. During follow-up, some ICD recipients experience the sensation of ICD discharge in the absence of an actual discharge (phantom shock). The aim of this study was to evaluate the incidence and predictors of phantom shocks in ICD recipients.Methods
Medical records of 629 consecutive patients with ischaemic or dilated cardiomyopathy and prior ICD implantation were studied.Results
With a median follow-up of 35 months, phantom shocks were reported by 5.1 % of ICD recipients (5.7 % in the primary prevention group and 3.7 % for the secondary prevention group; p=NS). In the combined group of primary and secondary prevention, there were no significant predictors of the occurrence of phantom shocks. However, in the primary prevention group, phantom shocks were related to a history of atrial fibrillation (p=0.03) and NYHA class <III (p=0.05). In the secondary prevention group, there were no significant predictors for phantom shocks.Conclusion
Phantom shocks occur in approximately 5 % of all ICD recipients. In primary prevention patients, a relation with a history of atrial fibrillation and NYHA class <III were significant predictors for the occurrence of phantom shocks. In the secondary prevention patients, no significant predictors were found. 相似文献5.
Pol Nadal-Jimenez Joanne S. Griffin Lianne Davies Crystal L. Frost Marco Marcello Gregory D. D. Hurst 《Environmental microbiology》2019,21(8):3172-3182
Maternally heritable symbionts are common in arthropods and represent important partners and antagonists. A major impediment to understanding the mechanistic basis of these symbioses has been lack of genetic manipulation tools, for instance, those enabling transgenic GFP expression systems for in vivo visualization. Here, we transform the ‘son-killer’ reproductive parasite Arsenophonus nasoniae that infects the parasitic wasp Nasonia vitripennis with the plasmid pOM1-gfp, re-introduce this strain to N. vitripennis and then used this system to track symbiont life history in vivo. These data revealed transfer of the symbiont into the fly pupa by N. vitripennis during oviposition and N. vitripennis larvae developing infection over time through feeding. A strong tropism of A. nasoniae to the N. vitripennis ovipositor developed during wasp pupation, which aids onward transmission. The symbiont was also visualized in diapause larvae. Occasional necrotic diapause larvae were observed which displayed intense systemic infection alongside widespread melanotic nodules indicative of an active but failed immune response. Our results provide the foundation for the study of this symbiosis through in vivo tracking of the fate of symbionts through host development, which is rarely achieved in heritable microbe/insect interactions. 相似文献
6.
Hae Yon Jeon Jinwook Choi Lianne Kraaier Young Hoon Kim David Eisenbarth Kijong Yi JuGyeong Kang Jin Woo Kim Hyo Sup Shim JooHyeon Lee DaeSik Lim 《The EMBO journal》2022,41(8)
Tissue homeostasis requires lineage fidelity of stem cells. Dysregulation of cell fate specification and differentiation leads to various diseases, yet the cellular and molecular mechanisms governing these processes remain elusive. We demonstrate that YAP/TAZ activation reprograms airway secretory cells, which subsequently lose their cellular identity and acquire squamous alveolar type 1 (AT1) fate in the lung. This cell fate conversion is mediated via distinctive transitional cell states of damage‐associated transient progenitors (DATPs), recently shown to emerge during injury repair in mouse and human lungs. We further describe a YAP/TAZ signaling cascade to be integral for the fate conversion of secretory cells into AT1 fate, by modulating mTORC1/ATF4‐mediated amino acid metabolism in vivo. Importantly, we observed aberrant activation of the YAP/TAZ‐mTORC1‐ATF4 axis in the altered airway epithelium of bronchiolitis obliterans syndrome, including substantial emergence of DATPs and AT1 cells with severe pulmonary fibrosis. Genetic and pharmacologic inhibition of mTORC1 activity suppresses lineage alteration and subepithelial fibrosis driven by YAP/TAZ activation, proposing a potential therapeutic target for human fibrotic lung diseases. 相似文献
7.
Metabotropic glutamate receptors (mGluRs) constitute an unique subclass of G protein-coupled receptors (GPCRs). These receptors are activated by the excitatory amino acid glutamate and play an essential role in regulating neural development and plasticity. In the present review, we overview the current understanding regarding the molecular mechanisms involved in the desensitization and endocytosis of Group 1 mGluRs as well as the relative contribution of desensitization to the spatial-temporal patterning of glutamate receptor signaling. Similar to what has been reported previously for prototypic GPCRs, mGluRs desensitization is mediated by second messenger-dependent protein kinases and GPCR kinases (GRKs). However, it remains to be determined whether mGluRs phosphorylation by GRKs and beta-arrestin binding are absolutely required for desensitization. Group 1 mGluRs endocytosis is both agonist-dependent and -independent. Agonist-dependent mGluRs internalization is mediated by a beta-arrestin- and dynamin-dependent clathrin-coated vesicle dependent endocytic pathway. The activation of Group 1 mGluRs also results in oscillatory Gq protein-coupling leading to the cyclical activation of phospholipase Cbeta thereby stimulating oscillations in both inositol 1,4,5-triphosphate formation and Ca(2+) release from intracellular stores. These glutamate receptor-stimulated Ca(2+) oscillations are translated into the synchronous activation of protein kinase C (PKC), which has led to the hypothesis that oscillatory mGluRs signaling involves the repetitive phosphorylation of mGluRs by PKC. However, recent experimental evidence suggests that oscillatory signaling is an intrinsic glutamate receptor property that is independent of feedback receptor phosphorylation by PKC. The challenge in the future will be to determine the structural determinants underlying mGluRs-mediated spatial-temporal signaling as well as to understand how complex signaling patterns can be interpreted by cells in both the developing and adult nervous systems. 相似文献
8.
Insights on bias and information in group-level studies 总被引:1,自引:0,他引:1
Sheppard L 《Biostatistics (Oxford, England)》2003,4(2):265-278
Ecological and aggregate data studies are examples of group-level studies. Even though the link between the predictors and outcomes is not preserved in these studies, inference about individual-level exposure effects is often a goal. The disconnection between the level of inference and the level of analysis expands the array of potential biases that can invalidate the inference from group-level studies. While several sources of bias, specifically due to measurement error and confounding, may be more complex in group-level studies, two sources of bias, cross-level and model specification bias, are a direct consequence of the disconnection. With the goal of aligning inference from individual versus group-level studies, I discuss the interplay between exposure and study design. I specify the additional assumptions necessary for valid inference, specifically that the between- and within-group exposure effects are equal. Then cross-level inference is possible. However, all the information in the group-level analysis comes from between-group comparisons. Models where the group-level analysis provides even a small percentage of information about the within-group exposure effect are most susceptible to model specification bias. Model specification bias can be even more serious when the group-level model isn't derived from an individual-level model. 相似文献
9.
Expression of Ca2+-permeable two-pore channels rescues NAADP signalling in TPC-deficient cells 下载免费PDF全文
Margarida Ruas Lianne C Davis Cheng-Chang Chen Anthony J Morgan Kai-Ting Chuang Timothy F Walseth Christian Grimm Clive Garnham Trevor Powell Nick Platt Frances M Platt Martin Biel Christian Wahl-Schott John Parrington Antony Galione 《The EMBO journal》2015,34(13):1743-1758
The second messenger NAADP triggers Ca2+ release from endo-lysosomes. Although two-pore channels (TPCs) have been proposed to be regulated by NAADP, recent studies have challenged this. By generating the first mouse line with demonstrable absence of both Tpcn1 and Tpcn2 expression (Tpcn1/2−/−), we show that the loss of endogenous TPCs abolished NAADP-dependent Ca2+ responses as assessed by single-cell Ca2+ imaging or patch-clamp of single endo-lysosomes. In contrast, currents stimulated by PI(3,5)P2 were only partially dependent on TPCs. In Tpcn1/2−/− cells, NAADP sensitivity was restored by re-expressing wild-type TPCs, but not by mutant versions with impaired Ca2+-permeability, nor by TRPML1. Another mouse line formerly reported as TPC-null likely expresses truncated TPCs, but we now show that these truncated proteins still support NAADP-induced Ca2+ release. High-affinity [32P]NAADP binding still occurs in Tpcn1/2−/− tissue, suggesting that NAADP regulation is conferred by an accessory protein. Altogether, our data establish TPCs as Ca2+-permeable channels indispensable for NAADP signalling. 相似文献
10.
Association studies in environmental statistics often involve exposure and outcome data that are misaligned in space. A common strategy is to employ a spatial model such as universal kriging to predict exposures at locations with outcome data and then estimate a regression parameter of interest using the predicted exposures. This results in measurement error because the predicted exposures do not correspond exactly to the true values. We characterize the measurement error by decomposing it into Berkson-like and classical-like components. One correction approach is the parametric bootstrap, which is effective but computationally intensive since it requires solving a nonlinear optimization problem for the exposure model parameters in each bootstrap sample. We propose a less computationally intensive alternative termed the "parameter bootstrap" that only requires solving one nonlinear optimization problem, and we also compare bootstrap methods to other recently proposed methods. We illustrate our methodology in simulations and with publicly available data from the Environmental Protection Agency. 相似文献