全文获取类型
收费全文 | 372篇 |
免费 | 34篇 |
专业分类
406篇 |
出版年
2023年 | 2篇 |
2022年 | 3篇 |
2021年 | 9篇 |
2020年 | 5篇 |
2019年 | 9篇 |
2018年 | 4篇 |
2017年 | 8篇 |
2016年 | 7篇 |
2015年 | 11篇 |
2014年 | 16篇 |
2013年 | 25篇 |
2012年 | 24篇 |
2011年 | 30篇 |
2010年 | 14篇 |
2009年 | 11篇 |
2008年 | 30篇 |
2007年 | 24篇 |
2006年 | 18篇 |
2005年 | 22篇 |
2004年 | 20篇 |
2003年 | 24篇 |
2002年 | 12篇 |
2001年 | 4篇 |
2000年 | 4篇 |
1999年 | 5篇 |
1998年 | 3篇 |
1997年 | 2篇 |
1996年 | 1篇 |
1995年 | 4篇 |
1994年 | 2篇 |
1993年 | 5篇 |
1992年 | 1篇 |
1991年 | 1篇 |
1990年 | 1篇 |
1989年 | 2篇 |
1988年 | 2篇 |
1987年 | 2篇 |
1986年 | 5篇 |
1985年 | 4篇 |
1983年 | 1篇 |
1981年 | 2篇 |
1980年 | 2篇 |
1979年 | 3篇 |
1978年 | 5篇 |
1977年 | 5篇 |
1976年 | 4篇 |
1974年 | 4篇 |
1973年 | 1篇 |
1972年 | 2篇 |
1967年 | 1篇 |
排序方式: 共有406条查询结果,搜索用时 15 毫秒
31.
The organelles of the exocytic pathway undergo a profound reorganization during the myogenic differentiation. Here, we have
investigated the dynamics of the membrane trafficking at various stages of the differentiation process by using the green
fluorescent protein-tagged, temperature-sensitive vesicular stomatitis virus G protein (tsG-GFP) as a marker. At the restrictive
temperature of 39°C, the tsG-GFP located to the endoplasmic reticulum (ER) at each stage of differentiation. Mobile membrane
containers moving from the ER to the Golgi elements were seen in myoblasts and myotubes upon shifting the temperature to 20°C.
In adult myofibers, in contrast, such containers were not seen although the tsG-GFP rapidly shifted from the ER to the Golgi
elements. The mobility of tsG-GFP in the myofiber ER was restricted, suggesting localization in an ER sub-compartment. Contrasting
with the ER-to-Golgi trafficking, transport from the Golgi elements to the plasma membrane involved mobile transport containers
in all differentiation stages. These findings indicate that ER-to-Golgi trafficking in adult skeletal myofibers does not involve
long-distance moving membrane carriers as occurs in other mammalian cell types. 相似文献
32.
Chlamydia pneumoniae is a common human respiratory pathogen, and sera from infected individuals recognize several proteins of C. pneumoniae. We produced C. pneumoniae-specific proteins in a Bacillus subtilis expression system. We then used these recombinant C. pneumoniae proteins and purified C. pneumoniae elementary bodies as antigens in enzyme immunoassays to assess the kinetics and protein specificity of the systemic and mucosal antibody responses induced by C. pneumoniae intranasal infection in BALB/c mice. The systemic antibodies in mice recognized strong 'key' immunogens of Chlamydia, Omp2 and Hsp60, but weakly targeted the MOMP protein, the major immunogen in chlamydial species other than C. pneumoniae. The IgA antibodies in bronchial secretions specifically recognized the putative surface protein of C. pneumoniae, Omp4. Our preliminary observations point to the necessity of further characterization of the mucosal antibody response during C. pneumoniae infection. 相似文献
33.
Biomimetic engineering of cellulose-based materials 总被引:1,自引:0,他引:1
Biomimetics is a field of science that investigates biological structures and processes for their use as models for the development of artificial systems. Biomimetic approaches have considerable potential in the development of new high-performance materials with low environmental impact. The cell walls of different plant species represent complex and highly sophisticated composite materials that can provide inspiration on how to design and fabricate lightweight materials with unique properties. Such materials can provide environmentally compatible solutions in advanced packaging, electronic devices, vehicles and sports equipment. This review gives an overview of the structures and interactions in natural plant cell walls and describes the first attempts towards mimicking them to develop novel biomaterials. 相似文献
34.
Structural organization and a standardized nomenclature for plant endo-1,4-beta-glucanases (cellulases) of glycosyl hydrolase family 9 下载免费PDF全文
35.
Riikka Jokinen Taina Lahtinen Paula Marttinen Maarit My?h?nen Pilvi Ruotsalainen Nicolas Yeung Antonina Shvetsova Alexander J. Kastaniotis J. Kalervo Hiltunen Tiina ?hman Tuula A. Nyman Hartmut Weiler Brendan J. Battersby 《Genetics》2015,200(1):221-235
Mammalian mitochondrial DNA (mtDNA) is a high-copy maternally inherited genome essential for aerobic energy metabolism. Mutations in mtDNA can lead to heteroplasmy, the co-occurence of two different mtDNA variants in the same cell, which can segregate in a tissue-specific manner affecting the onset and severity of mitochondrial dysfunction. To investigate mechanisms regulating mtDNA segregation we use a heteroplasmic mouse model with two polymorphic neutral mtDNA haplotypes (NZB and BALB) that displays tissue-specific and age-dependent selection for mtDNA haplotypes. In the hematopoietic compartment there is selection for the BALB mtDNA haplotype, a phenotype that can be modified by allelic variants of Gimap3. Gimap3 is a tail-anchored member of the GTPase of the immunity-associated protein (Gimap) family of protein scaffolds important for leukocyte development and survival. Here we show how the expression of two murine Gimap3 alleles from Mus musculus domesticus and M. m. castaneus differentially affect mtDNA segregation. The castaneus allele has incorporated a uORF (upstream open reading frame) in-frame with the Gimap3 mRNA that impairs translation and imparts a negative effect on the steady-state protein abundance. We found that quantitative changes in the expression of Gimap3 and the paralogue Gimap5, which encodes a lysosomal protein, affect mtDNA segregation in the mouse hematopoietic tissues. We also show that Gimap3 localizes to the endoplasmic reticulum and not mitochondria as previously reported. Collectively these data show that the abundance of protein scaffolds on the endoplasmic reticulum and lysosomes are important to the segregation of the mitochondrial genome in the mouse hematopoietic compartment. 相似文献
36.
Regan EA Mazur W Meoni E Toljamo T Millar J Vuopala K Bowler RP Rahman I Nicks ME Crapo JD Kinnula VL 《Free radical biology & medicine》2011,51(3):726-732
Extracellular superoxide dismutase (ECSOD) is the major superoxide-scavenging enzyme in the lung. Certain ECSOD polymorphisms are protective against COPD. We postulated that smokers and COPD subjects would have altered levels of ECSOD in the lung, airway secretions, and/or plasma. Lung tissue ECSOD was evaluated from nonsmokers, smokers, and subjects with mild to very severe COPD by Western blot, immunohistochemistry, and ELISA. ECSOD levels in plasma, bronchoalveolar lavage fluid (BALF), and induced-sputum supernatants were analyzed by ELISA and correlated with smoking history and disease status. Immunohistochemistry identified ECSOD in extracellular matrix around bronchioles, arteries, and alveolar walls, with decreases seen in the interstitium and vessels of severe COPD subjects using digital image analysis. Plasma ECSOD did not differ between COPD subjects and controls nor based on smoking status. ECSOD levels in induced sputum supernatants were elevated in current smokers and especially in COPD subjects compared to nonsmokers, whereas corresponding changes could not be seen in the BALF. ECSOD expression was reduced around vessels and bronchioles in COPD lungs. Substantial increases in sputum ECSOD in smokers and COPD is interpreted as an adaptive response to increased oxidative stress and may be a useful biomarker of disease activity in COPD. 相似文献
37.
Szyniarowski P Corcelle-Termeau E Farkas T Høyer-Hansen M Nylandsted J Kallunki T Jäättelä M 《Autophagy》2011,7(8):892-903
Macroautophagy is a catabolic process that maintains cellular homeostasis and protects cells against various external stresses including starvation. Except for the identification of the Akt-mTORC1 pathway as a major negative regulator, little is known about signaling networks that control macroautophagy under optimal growth conditions. Therefore, we screened a human kinome siRNA library for siRNAs that increase the number of autophagosomes in normally growing MCF-7 human breast carcinoma cells, and identified 10 kinases as regulators of constitutive macroautophagy. Further analysis of these kinases with respect to the autophagic flux, kinase signaling and endolysosomal function identified WNK2 as a positive regulator of autophagosome maturation and nine others as macroautophagy inhibitors. The depletion of MK2, PACSIN1, DAPK2, CDKL3 and SCYL1 functioned upstream of Akt-mTORC1 pathway, whereas CSNK1A1, BUB1, PKLR and NEK4 suppressed autophagosome formation downstream or independent of mTORC1. Importantly, all identified kinases except for BUB1 regulated macroautophagy also in immortalized MCF-10A breast epithelial cells. The kinases identified here shed light to the complex regulation of macroautophagy and open new possibilities for its pharmacological manipulation. 相似文献
38.
Nassa G Tarallo R Ambrosino C Bamundo A Ferraro L Paris O Ravo M Guzzi PH Cannataro M Baumann M Nyman TA Nola E Weisz A 《Proteomics》2011,11(1):159-165
Estrogen receptors α (ER-α) and β (ER-β) play distinct biological roles in onset and progression of hormone-responsive breast cancer, with ER-β exerting a modulatory activity on ER-α-mediated estrogen signaling and stimulation of cell proliferation by mechanisms still not fully understood. We stably expressed human ER-β fused to a tandem affinity purification-tag in estrogen-responsive MCF-7 cells and applied tandem affinity purification and nanoLC-MS/MS to identify the ER-β interactome of this cell type. Functional annotation by bioinformatics analyses of the 303 proteins that co-purify with ER-β from nuclear extracts identify several new molecular partners of this receptor subtype that represents nodal points of a large protein network controlling multiple processes and functions in breast cancer cells. 相似文献
39.
Background
To better understand the complex molecular level interactions seen in the pathogenesis of Alzheimer''s disease, the results of the wet-lab and clinical studies can be complemented by mathematical models. Astrocytes are known to become reactive in Alzheimer''s disease and their ionic equilibrium can be disturbed by interaction of the released and accumulated transmitters, such as serotonin, and peptides, including amyloid- peptides (A). We have here studied the effects of small amounts of A25–35 fragments on the transmitter-induced calcium signals in astrocytes by Fura-2AM fluorescence measurements and running simulations of the detected calcium signals.Methodology/Principal Findings
Intracellular calcium signals were measured in cultured rat cortical astrocytes following additions of serotonin and glutamate, or either of these transmitters together with A25–35. A25–35 increased the number of astrocytes responding to glutamate and exceedingly increased the magnitude of the serotonin-induced calcium signals. In addition to A25–35-induced effects, the contribution of intracellular calcium stores to calcium signaling was tested. When using higher stimulus frequency, the subsequent calcium peaks after the initial peak were of lower amplitude. This may indicate inadequate filling of the intracellular calcium stores between the stimuli. In order to reproduce the experimental findings, a stochastic computational model was introduced. The model takes into account the major mechanisms known to be involved in calcium signaling in astrocytes. Model simulations confirm the principal experimental findings and show the variability typical for experimental measurements.Conclusions/Significance
Nanomolar A25–35 alone does not cause persistent change in the basal level of calcium in astrocytes. However, even small amounts of A25–35, together with transmitters, can have substantial synergistic effects on intracellular calcium signals. Computational modeling further helps in understanding the mechanisms associated with intracellular calcium oscillations. Modeling the mechanisms is important, as astrocytes have an essential role in regulating the neuronal microenvironment of the central nervous system. 相似文献40.
Niskanen E Könönen M Määttä S Hallikainen M Kivipelto M Casarotto S Massimini M Vanninen R Mervaala E Karhu J Soininen H 《PloS one》2011,6(10):e26113