全文获取类型
收费全文 | 145篇 |
免费 | 16篇 |
出版年
2022年 | 6篇 |
2021年 | 5篇 |
2020年 | 2篇 |
2019年 | 2篇 |
2018年 | 6篇 |
2017年 | 5篇 |
2015年 | 12篇 |
2014年 | 10篇 |
2013年 | 9篇 |
2012年 | 14篇 |
2011年 | 10篇 |
2010年 | 6篇 |
2009年 | 5篇 |
2008年 | 3篇 |
2007年 | 6篇 |
2006年 | 5篇 |
2005年 | 4篇 |
2004年 | 9篇 |
2003年 | 2篇 |
2002年 | 8篇 |
2001年 | 3篇 |
2000年 | 3篇 |
1999年 | 3篇 |
1997年 | 1篇 |
1996年 | 2篇 |
1995年 | 1篇 |
1994年 | 2篇 |
1991年 | 2篇 |
1990年 | 2篇 |
1989年 | 2篇 |
1986年 | 1篇 |
1985年 | 2篇 |
1981年 | 1篇 |
1978年 | 2篇 |
1975年 | 2篇 |
1965年 | 1篇 |
1909年 | 2篇 |
排序方式: 共有161条查询结果,搜索用时 62 毫秒
61.
62.
Sandra Da Costa Nathalie M.-P. Bourquin Jean-Fran?ois Knebel Melissa Saenz Wietske van der Zwaag Stephanie Clarke 《PloS one》2015,10(5)
Environmental sounds are highly complex stimuli whose recognition depends on the interaction of top-down and bottom-up processes in the brain. Their semantic representations were shown to yield repetition suppression effects, i. e. a decrease in activity during exposure to a sound that is perceived as belonging to the same source as a preceding sound. Making use of the high spatial resolution of 7T fMRI we have investigated the representations of sound objects within early-stage auditory areas on the supratemporal plane. The primary auditory cortex was identified by means of tonotopic mapping and the non-primary areas by comparison with previous histological studies. Repeated presentations of different exemplars of the same sound source, as compared to the presentation of different sound sources, yielded significant repetition suppression effects within a subset of early-stage areas. This effect was found within the right hemisphere in primary areas A1 and R as well as two non-primary areas on the antero-medial part of the planum temporale, and within the left hemisphere in A1 and a non-primary area on the medial part of Heschl’s gyrus. Thus, several, but not all early-stage auditory areas encode the meaning of environmental sounds. 相似文献
63.
Vanusa Manfredini Giovana Brondani Biancini Camila Simioni Vanzin Anna Maria Ribeiro Dal Vesco Franciele Cipriani Lidiana Biasi Roberta Treméa Marion Deon Maria do Carmo Ruaro Peralba Moacir Wajner Carmen Regla Vargas 《Cell biochemistry and function》2010,28(5):360-366
Type 2 diabetes (T2D) is associated with increased oxidative stress as indicated by elevated levels of lipid peroxidation and protein oxidation products. Since reactive oxygen species (ROS) can cause damage to biological macromolecules including DNA, this study investigated oxidative damage to DNA using the alkaline (pH > 13) comet assay in peripheral whole blood leukocytes sampled from 15 dyslipidemic T2D patients treated with simvastatin (20 mg/day), 15 dyslipidemic T2D patients not treated with simvastatin, 20 non‐dyslipidemic T2D patients, and 20 healthy individuals (controls). Our results showed a greater DNA migration in terms of damage index (DI) (p < 0.01) in the dyslipidemic T2D patients not treated with statin (DI = 67.70 ± 10.89) when compared to the dyslipidemic T2D patients under statin treatment (DI = 47.56 ± 7.02), non‐dyslipidemic T2D patients (DI = 52.25 ± 9.14), and controls (DI = 13.20 ± 6.40). Plasma malondialdehyde (MDA) and C‐reactive protein (CRP) levels were also increased and total antioxidant reactivity (TAR) and paraoxonase activity (PON1) decreased in non‐dyslipidemic T2D patients and dyslipidemic T2D non‐treated with simvastatin. We also found that DI was inversely correlated with TAR (r = ?0.61, p < 0.05) and PON1 (r = ?0.67, p < 0.01). In addition, there was a significant positive correlation between DI and CRP (r = 0.80, p < 0.01). Our results therefore indicate that simvastatin treatment plays a protective role on oxidative damage to DNA in dyslipidemic T2D patients probably reflecting a general decrease in oxidative stress in these patients. Copyright © 2010 John Wiley & Sons, Ltd. 相似文献
64.
Paola de Andrade Mello Eduardo Cremonese Filippi-Chiela Jéssica Nascimento Aline Beckenkamp Danielle Bertodo Santana Franciele Kipper Emerson André Casali Alessandra Nejar Bruno Juliano Domiraci Paccez Luiz Fernando Zerbini Marcia Rosangela Wink Guido Lenz Andréia Buffon 《Molecular biology of the cell》2014,25(19):2905-2918
In cervical cancer, HPV infection and disruption of mechanisms involving cell growth, differentiation, and apoptosis are strictly linked with tumor progression and invasion. Tumor microenvironment is ATP and adenosine rich, suggesting a role for purinergic signaling in cancer cell growth and death. Here we investigate the effect of extracellular ATP on human cervical cancer cells. We find that extracellular ATP itself has a small cytotoxic effect, whereas adenosine formed from ATP degradation by ectonucleotidases is the main factor responsible for apoptosis induction. The level of P2×7 receptor seemed to define the main cytotoxic mechanism triggered by ATP, since ATP itself eliminated a small subpopulation of cells that express high P2×7 levels, probably through its activation. Corroborating these data, blockage or knockdown of P2×7 only slightly reduced ATP cytotoxicity. On the other hand, cell viability was almost totally recovered with dipyridamole, an adenosine transporter inhibitor. Moreover, ATP-induced apoptosis and signaling—p53 increase, AMPK activation, and PARP cleavage—as well as autophagy induction were also inhibited by dipyridamole. In addition, inhibition of adenosine conversion into AMP also blocked cell death, indicating that metabolization of intracellular adenosine originating from extracellular ATP is responsible for the main effects of the latter in human cervical cancer cells. 相似文献
65.
Sonja Hartwig Silja Raschke Birgit Knebel Mika Scheler Martin Irmler Waltraud Passlack Stefan Muller Franz-Georg Hanisch Thomas Franz Xinping Li Hans-Dieter Dicken Kristin Eckardt Johannes Beckers Martin Hrabe de Angelis Cora Weigert Hans-Ulrich Häring Hadi Al-Hasani D. Margriet Ouwens Jürgen Eckel Jorg Kotzka Stefan Lehr 《Biochimica et Biophysica Acta - Proteins and Proteomics》2014,1844(5):1011-1017
The skeletal muscle is a metabolically active tissue that secretes various proteins. These so-called myokines have been proposed to affect muscle physiology and to exert systemic effects on other tissues and organs. Yet, changes in the secretory profile may participate in the pathophysiology of metabolic diseases. The present study aimed at characterizing the secretome of differentiated primary human skeletal muscle cells (hSkMC) derived from healthy, adult donors combining three different mass spectrometry based non-targeted approaches as well as one antibody based method. This led to the identification of 548 non-redundant proteins in conditioned media from hSkmc. For 501 proteins, significant mRNA expression could be demonstrated. Applying stringent consecutive filtering using SignalP, SecretomeP and ER_retention signal databases, 305 proteins were assigned as potential myokines of which 12 proteins containing a secretory signal peptide were not previously described. This comprehensive profiling study of the human skeletal muscle secretome expands our knowledge of the composition of the human myokinome and may contribute to our understanding of the role of myokines in multiple biological processes. This article is part of a Special Issue entitled: Biomarkers: A Proteomic Challenge. 相似文献
66.
Miriam Reuschenbach Magnus von Knebel Doeberitz Nicolas Wentzensen 《Cancer immunology, immunotherapy : CII》2009,58(10):1535-1544
This review summarizes studies on humoral immune responses against tumor-associated antigens (TAAs) with a focus on antibody
frequencies and the potential diagnostic, prognostic, and etiologic relevance of antibodies against TAAs. We performed a systematic
literature search in Medline and identified 3,619 articles on humoral immune responses and TAAs. In 145 studies, meeting the
inclusion criteria, humoral immune responses in cancer patients have been analyzed against over 100 different TAAs. The most
frequently analyzed antigens were p53, MUC1, NY-ESO-1, c-myc, survivin, p62, cyclin B1, and Her2/neu. Antibodies against these TAAs were detected in 0–69% (median 14%) of analyzed tumor patients. Antibody frequencies were
generally very low in healthy individuals, with the exception of few TAAs, especially MUC1. For several TAAs, including p53,
Her2/neu, and NY-ESO-1, higher antibody frequencies were reported when tumors expressed the respective TAA. Antibodies against
MUC1 were associated with a favorable prognosis while antibodies against p53 were associated with poor disease outcome. These
data suggest different functional roles of endogenous antibodies against TAAs. Although data on prediagnostic antibody levels
are scarce and antibody frequencies for most TAAs are at levels precluding use in diagnostic assays for cancer early detection,
there is some promising data on achieving higher sensitivity for cancer detection using panels of TAAs.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
67.
Cell migration through small gaps 总被引:1,自引:0,他引:1
Brunner CA Ehrlicher A Kohlstrunk B Knebel D Käs JA Goegler M 《European biophysics journal : EBJ》2006,35(8):713-719
Cell motility is a fundamental process associated with many phenomena in nature, such as immune response, wound healing, and cancer metastasis. In these processes, cells must squeeze through cell layers, and we characterize this ability to actively produce forces and simultaneously adapt their shapes. We have measured forward forces up to 15 nN that a migrating keratocyte was able to generate, in order to adjust its shape and successfully force its way under and past an obstacle. We also observed that 34 nN was capable of stalling the cell’s forward motion. Furthermore, we measured that under compression stresses up to 1,165 pN/μm2 (1,165 Pa), cell morphology, and velocity remained unchanged. Additionally, we found that keratocytes were able to compress themselves up to 80% vertically in order to squeeze through a gap as small as 500 nm.Authors Claudia A. Brunner, Allen Ehrlicher, and Michael Goegler have contributed equally to this work. 相似文献
68.
Christoph Melzer Fabian Knebel Bruno Ismer Hansjürgen Bondke Christoph A Nienaber Gert Baumann Adrian C Borges 《Cardiovascular ultrasound》2006,4(1):1-6
The severity index is a new echocardiographic measure that is thought to be an accurate indicator of aortic leaflet pathology in patients with AS. However, it has not been validated against cardiac catheterization or Doppler echocardiographic measures of AS severity nor has it been applied to patients with aortic sclerosis. The purposes of this study were to compare the severity index to invasive hemodynamics and Doppler echocardiography across the spectrum of calcific aortic valve disease, including aortic sclerosis and AS. 48 patients with aortic sclerosis and AS undergoing echocardiography and cardiac catheterization comprised the study population. The aortic valve leaflets were assessed for mobility (scale 1 to 6) and calcification (scale 1 to 4) and the severity index was calculated as the sum of the mobility and calcification scores according to the methods of Bahler et al. The severity index increased with increasing severity of aortic valve disease; the severity indices for patients with aortic sclerosis, mild to moderate AS and severe AS were 3.38 ± 1.06, 6.45 ± 2.16 and 8.38 ± 1.41, respectively. The aortic jet velocity by echocardiography and the square root of the maximum aortic valve gradient by cardiac catheterization correlated well with the severity index (r = 0.84, p < 0.0001; r = 0.84, p < 0.0001, respectively). These results confirm that the severity index correlates with hemodynamic severity of aortic valve disease and may prove to be a useful measure in patients with aortic sclerosis and AS. 相似文献
69.
70.
?ngela Zanatta Alana Pimentel Moura Anelise Miotti Tonin Lisiane Aur��lio Knebel Mateus Grings Vannessa Ara��jo Lobato C��sar Augusto Jo?o Ribeiro Carlos Severo Dutra-Filho Guilhian Leipnitz Moacir Wajner 《Cellular and molecular neurobiology》2013,33(1):137-146
Isolated 3-methylcrotonyl-CoA carboxylase deficiency (3MCCD) is an autosomal recessive disorder of leucine metabolism biochemically characterized by accumulation of 3-methylcrotonylglycine (3MCG), 3-methylcrotonic acid (3MCA) and 3-hydroxyisovaleric acid. A considerable number of affected individuals present neurological symptoms with or without precedent crises of metabolic decompensation and brain abnormalities whose pathogenesis is poorly known. We investigated the in vitro effects of 3MCG and 3MCA on important parameters of oxidative stress in cerebral cortex of young rats. 3MCG and 3MCA significantly increased TBA-RS and carbonyl formation, indicating that these compounds provoke lipid and protein oxidation, respectively. In contrast, nitric oxide production was not affected by 3MCG and 3MCA. Furthermore, 3MCG- and 3MCA-induced elevation of TBA-RS values was fully prevented by melatonin, trolox and reduced glutathione, but not by the nitric oxide inhibitor N??-nitro-l-arginine methyl ester or the combination of catalase plus superoxide dismutase, indicating that reactive oxygen species were involved in the oxidative damage caused by these compounds. We also found that the activity of the antioxidant enzymes glutathione peroxidase, catalase, superoxide dismutase and glutathione reductase were not altered in vitro by 3MCG and 3MCA. It is therefore presumed that alterations of the cellular redox homeostasis caused by the major metabolites accumulating in 3MCCD may potentially be involved in the pathophysiology of the neurological dysfunction and structural brain alterations found in patients affected by this disorder. 相似文献