全文获取类型
收费全文 | 278篇 |
免费 | 32篇 |
出版年
2023年 | 1篇 |
2021年 | 6篇 |
2020年 | 4篇 |
2019年 | 4篇 |
2018年 | 7篇 |
2017年 | 6篇 |
2016年 | 8篇 |
2015年 | 19篇 |
2014年 | 8篇 |
2013年 | 22篇 |
2012年 | 24篇 |
2011年 | 14篇 |
2010年 | 9篇 |
2009年 | 12篇 |
2008年 | 22篇 |
2007年 | 16篇 |
2006年 | 11篇 |
2005年 | 19篇 |
2004年 | 16篇 |
2003年 | 10篇 |
2002年 | 14篇 |
2001年 | 10篇 |
2000年 | 9篇 |
1999年 | 4篇 |
1998年 | 5篇 |
1997年 | 3篇 |
1996年 | 2篇 |
1993年 | 2篇 |
1992年 | 5篇 |
1991年 | 1篇 |
1990年 | 2篇 |
1989年 | 2篇 |
1988年 | 2篇 |
1986年 | 1篇 |
1985年 | 1篇 |
1984年 | 2篇 |
1982年 | 1篇 |
1973年 | 1篇 |
1967年 | 2篇 |
1966年 | 1篇 |
1918年 | 1篇 |
1916年 | 1篇 |
排序方式: 共有310条查询结果,搜索用时 15 毫秒
1.
2.
3.
R. Al Nazer A. Klodowski T. Rantalainen A. Heinonen H. Sievänen A. Mikkola 《Computer methods in biomechanics and biomedical engineering》2013,16(6):573-579
Load-induced strains applied to bone can stimulate its development and adaptation. In order to quantify the incident strains within the skeleton, in vivo implementation of strain gauges on the surfaces of bone is typically used. However, in vivo strain measurements require invasive methodology that is challenging and limited to certain regions of superficial bones only such as the anterior surface of the tibia. Based on our previous study [Al Nazer et al. (2008) J Biomech. 41:1036–1043], an alternative numerical approach to analyse in vivo strains based on the flexible multibody simulation approach was proposed. The purpose of this study was to extend the idea of using the flexible multibody approach in the analysis of bone strains during physical activity through integrating the magnetic resonance imaging (MRI) technique within the framework. In order to investigate the reliability and validity of the proposed approach, a three-dimensional full body musculoskeletal model with a flexible tibia was used as a demonstration example. The model was used in a forward dynamics simulation in order to predict the tibial strains during walking on a level exercise. The flexible tibial model was developed using the actual geometry of human tibia, which was obtained from three-dimensional reconstruction of MRI. Motion capture data obtained from walking at constant velocity were used to drive the model during the inverse dynamics simulation in order to teach the muscles to reproduce the motion in the forward dynamics simulation. Based on the agreement between the literature-based in vivo strain measurements and the simulated strain results, it can be concluded that the flexible multibody approach enables reasonable predictions of bone strain in response to dynamic loading. The information obtained from the present approach can be useful in clinical applications including devising exercises to prevent bone fragility or to accelerate fracture healing. 相似文献
4.
Satu Mikkola Mikko Oivanen Kari Neuvonen Suvi Piitari Kaisa Ketomäki Harri Lönnberg 《Nucleosides, nucleotides & nucleic acids》2013,32(10-12):1675-1692
Abstract Uridylyl-(3′,5′)-8-carboxymethylaminoadenosine has been synthesised, and its transesterification to uridine 2′,3′-cyclic phosphate in the presence and absence of Zn2+ ion has been studied. The results show that a carboxylate function in the vicinity of the phosphodiester bond accelerates the metal ion promoted cleavage but not the metal ion independent reaction. Under acidic conditions, the predominant reaction is the cleavage of the side chain, giving the 8-amino derivative. 相似文献
5.
N. Belén Rumie Vittar María Julia Lamberti María Florencia Pansa Renzo E. Vera M. Exequiel RodriguezI. Sol Cogno Laura N. Milla SanabriaViviana A. Rivarola 《生物化学与生物物理学报:癌评论》2013
As with natural ecosystems, species within the tumor microenvironment are connected by pairwise interactions (e.g. mutualism, predation) leading to a strong interdependence of different populations on each other. In this review we have identified the ecological roles played by each non-neoplastic population (macrophages, endothelial cells, fibroblasts) and other abiotic components (oxygen, extracellular matrix) directly involved with neoplastic development. A way to alter an ecosystem is to affect other species within the environment that are supporting the growth and survival of the species of interest, here the tumor cells; thus, some features of ecological systems could be exploited for cancer therapy. We propose a well-known antitumor therapy called photodynamic therapy (PDT) as a novel modulator of ecological interactions. We refer to this as “ecological photodynamic therapy.” The main goal of this new strategy is the improvement of therapeutic efficiency through the disruption of ecological networks with the aim of destroying the tumor ecosystem. It is therefore necessary to identify those interactions from which tumor cells get benefit and those by which it is impaired, and then design multitargeted combined photodynamic regimes in order to orchestrate non-neoplastic populations against their neoplastic counterpart. Thus, conceiving the tumor as an ecological system opens avenues for novel approaches on treatment strategies. 相似文献
6.
Michael?R. Knowles Margaret?W. Leigh Lawrence?E. Ostrowski Lu Huang Johnny?L. Carson Milan?J. Hazucha Weining Yin Jonathan?S. Berg Stephanie?D. Davis Sharon?D. Dell Thomas?W. Ferkol Margaret Rosenfeld Scott?D. Sagel Carlos?E. Milla Kenneth?N. Olivier Emily?H. Turner Alexandra?P. Lewis Michael?J. Bamshad Deborah?A. Nickerson Jay Shendure Maimoona?A. Zariwala the Genetic Disorders of Mucociliary Clearance?Consortium 《American journal of human genetics》2013,92(1):99-106
Primary ciliary dyskinesia (PCD) is a genetically heterogeneous, autosomal-recessive disorder, characterized by oto-sino-pulmonary disease and situs abnormalities. PCD-causing mutations have been identified in 14 genes, but they collectively account for only ∼60% of all PCD. To identify mutations that cause PCD, we performed exome sequencing on six unrelated probands with ciliary outer dynein arm (ODA) defects. Mutations in CCDC114, an ortholog of the Chlamydomonas reinhardtii motility gene DCC2, were identified in a family with two affected siblings. Sanger sequencing of 67 additional individuals with PCD with ODA defects from 58 families revealed CCDC114 mutations in 4 individuals in 3 families. All 6 individuals with CCDC114 mutations had characteristic oto-sino-pulmonary disease, but none had situs abnormalities. In the remaining 5 individuals with PCD who underwent exome sequencing, we identified mutations in two genes (DNAI2, DNAH5) known to cause PCD, including an Ashkenazi Jewish founder mutation in DNAI2. These results revealed that mutations in CCDC114 are a cause of ciliary dysmotility and PCD and further demonstrate the utility of exome sequencing to identify genetic causes in heterogeneous recessive disorders. 相似文献
7.
8.
9.
Neuronal localization of the TNFalpha converting enzyme (TACE) in brain tissue and its correlation to amyloid plaques 总被引:6,自引:0,他引:6
The tumor necrosis factor (TNF)-alpha converting enzyme (TACE) can cleave the cell-surface ectodomain of the amyloid-beta precursor protein (APP), thus decreasing the generation of amyloid-beta (Abeta) by cultured non-neuronal cells. While the amyloidogenic processing of APP in neurons is linked to the pathogenesis of Alzheimer's disease (AD), the expression of TACE in neurons has not yet been examined. Thus, we assessed TACE expression in a series of neuronal and non-neuronal cell types by Western blots. We found that TACE was present in neurons and was only faintly detectable in lysates of astrocytes, oligodendrocytes, and microglial cells. Immunohistochemical analysis was used to determine the cellular localization of TACE in the human brain, and its expression was detected in distinct neuronal populations, including pyramidal neurons of the cerebral cortex and granular cell layer neurons in the hippocampus. Very low levels of TACE were seen in the cerebellum, with Purkinje cells at the granular-molecular boundary staining faintly. Because TACE was localized predominantly in areas of the brain that are affected by amyloid plaques in AD, we examined its expression in a series of AD brains. We found that AD and control brains showed similar levels of TACE staining, as well as similar patterns of TACE expression. By double labeling for Abeta plaques and TACE, we found that TACE-positive neurons often colocalized with amyloid plaques in AD brains. These observations support a neuronal role for TACE and suggest a mechanism for its involvement in AD pathogenesis as an antagonist of Abeta formation. 相似文献
10.