全文获取类型
收费全文 | 603篇 |
免费 | 47篇 |
国内免费 | 61篇 |
出版年
2024年 | 3篇 |
2023年 | 17篇 |
2022年 | 42篇 |
2021年 | 52篇 |
2020年 | 31篇 |
2019年 | 45篇 |
2018年 | 39篇 |
2017年 | 17篇 |
2016年 | 32篇 |
2015年 | 31篇 |
2014年 | 46篇 |
2013年 | 54篇 |
2012年 | 48篇 |
2011年 | 44篇 |
2010年 | 18篇 |
2009年 | 18篇 |
2008年 | 25篇 |
2007年 | 16篇 |
2006年 | 10篇 |
2005年 | 23篇 |
2004年 | 16篇 |
2003年 | 14篇 |
2002年 | 15篇 |
2001年 | 12篇 |
2000年 | 2篇 |
1999年 | 4篇 |
1998年 | 3篇 |
1996年 | 5篇 |
1995年 | 2篇 |
1993年 | 2篇 |
1992年 | 1篇 |
1991年 | 1篇 |
1990年 | 3篇 |
1989年 | 4篇 |
1987年 | 3篇 |
1986年 | 3篇 |
1985年 | 1篇 |
1984年 | 4篇 |
1983年 | 2篇 |
1981年 | 1篇 |
1974年 | 1篇 |
1970年 | 1篇 |
排序方式: 共有711条查询结果,搜索用时 15 毫秒
151.
Heterogeneous Distribution of Sodium for High Thermoelectric Performance of p‐type Multiphase Lead‐Chalcogenides 下载免费PDF全文
Sima Aminorroaya Yamini David R. G. Mitchell Zachary M. Gibbs Rafael Santos Vaughan Patterson Sean Li Yan Zhong Pei Shi Xue Dou G. Jeffrey Snyder 《Liver Transplantation》2015,5(21)
Despite the effectiveness of sodium as a p‐type dopant for lead chalcogenides, its solubility is shown to be very limited in these hosts. Here, a high thermoelectric efficiency of ≈2 over a wide temperature range is reported in multiphase quaternary (PbTe)0.65(PbS)0.25(PbSe)0.1 compounds that are doped with sodium at concentrations greater than the solubility limits of the matrix. Although these compounds present room temperature thermoelectric efficiencies similar to sodium doped PbTe, a dramatically enhanced Hall carrier mobility at temperatures above 600 K for heavily doped compounds results in significantly enhanced thermoelectric efficiencies at elevated temperatures. This is achieved through the composition modulation doping mechanism resulting from heterogeneous distribution of the sodium dopant between precipitates and the matrix at elevated temperatures. These results can lead to further advances in designing high performance multiphase thermoelectric materials with intrinsically heterogeneous dopant distributions. 相似文献
152.
Foam cell‐derived 4‐hydroxynonenal induces endothelial cell senescence in a TXNIP‐dependent manner 下载免费PDF全文
Yael Riahi Nurit Kaiser Guy Cohen Ihab Abd‐Elrahman Galia Blum Oz M. Shapira Tomer Koler Maya Simionescu Anca V. Sima Neven Zarkovic Kamelija Zarkovic Marica Orioli Giancarlo Aldini Erol Cerasi Gil Leibowitz Shlomo Sasson 《Journal of cellular and molecular medicine》2015,19(8):1887-1899
Vascular endothelial cell (VEC) senescence is considered an early event in the development of atherosclerotic lesions. Stressful stimuli, in particular oxidative stress, have been linked to premature senescence in the vasculature. Foam cells are a major source of reactive oxygen species and may play a role in the induction of VEC senescence; hence, we investigated their involvement in the induction of VEC senescence in a co‐culture transwell system. Primary bovine aortic endothelial cells, exposed to the secretome of THP‐1 monocyte‐derived foam cells, were analysed for the induction of senescence. Senescence associated β‐galactosidase activity and the expression of p16 and p21 were increased, whereas phosphorylated retinoblastoma protein was reduced. This senescent phenotype was mediated by 4‐hydroxnonenal (4‐HNE), a lipid peroxidation product secreted from foam cells; scavenging of 4‐HNE in the co‐culture medium blunted this effect. Furthermore, both foam cells and 4‐HNE increased the expression of the pro‐oxidant thioredoxin‐interacting protein (TXNIP). Molecular manipulation of TXNIP expression confirmed its involvement in foam cell‐induced senescence. Previous studies showed that peroxisome proliferator‐activated receptor (PPAR)δ was activated by 4‐hydroalkenals, such as 4‐HNE. Pharmacological interventions supported the involvement of the 4‐HNE‐PPARδ axis in the induction of TXNIP and VEC senescence. The association of TXNIP with VEC senescence was further supported by immunofluorescent staining of human carotid plaques in which the expression of both TXNIP and p21 was augmented in endothelial cells. Collectively, these findings suggest that foam cell‐released 4‐HNE activates PPARδ in VEC, leading to increased TXNIP expression and consequently to senescence. 相似文献
153.
By using of structure-based virtual screening, 13 novel epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors were discovered from 197,116 compounds in the SPECS database here. Among them, 8 compounds significantly inhibited EGFR kinase activity with IC(50) values lower than 10 μM. 3-{[1-(3-Chloro-4-fluorophenyl)-3,5-dioxo-4-pyrazolidinylidene]methyl}phenyl 2-thiophenecarboxylate (13), particularly, was the most potent inhibitor possessing the IC(50) value of 3.5 μM. The docking studies also provide some useful information that the docking models of the 13 compounds are beneficial to find a new path for designing novel EGFR inhibitors. 相似文献
154.
Vadolas J Nefedov M Wardan H Mansooriderakshan S Voullaire L Jamsai D Williamson R Ioannou PA 《The Journal of biological chemistry》2006,281(11):7399-7405
Splicing mutations are common causes of beta-thalassemia. Some splicing mutations permit normal splicing as well as aberrant splicing, which can give a reduced level of normal beta-globin synthesis causing mild disease (thalassemia intermedia). For other mutations, normal splicing is reduced to low levels, and patients are transfusion-dependent when homozygous for the disease. The development of therapies for beta-thalassemia will require suitable mouse models for preclinical studies. In this study, we report the generation of a humanized mouse model carrying the common IVSI-110 splicing mutation on a BAC including the human beta-globin ((hu)beta-globin) locus. We examined heterozygous murine beta-globin knock-out mice ((mu)beta(th-3/+)) carrying either the IVSI-110 or the normal (hu)beta-globin locus. Our results show a 90% decrease in (hu)beta-globin chain synthesis in the IVSI-110 mouse model compared with the mouse model carrying the normal (hu)beta-globin locus. This notable difference is attributed to aberrant splicing. The humanized IVSI-110 mouse model accurately recapitulates the splicing defect found in comparable beta-thalassemia patients. This mouse model is available as a platform for testing strategies for the restoration of normal splicing. 相似文献
155.
Yang Y Guo J Liu Z Tang S Li N Yang M Pang Q Fan F Bu J Yuan ST Xiao X Chen Y Zhao K 《Human genetics》2006,120(1):144-147
Accessory auricular anomaly is a small excrescence of skin that contains elastic cartilage on different regions of the helix and the face. Previous work has shown that the genetic trait of some patients with the isolated symptom of accessory auricular anomaly is autosomal dominant. To map the gene for autosomal dominant accessory auricular anomaly (ADAAA), we investigated a Chinese family with 11 affected individuals. We performed linkage analysis with microsatellite markers spanning the whole human-genome in the family. The inheritance pattern of the ADAAA family was autosomal dominant with complete penetrance. Two-point linkage analysis revealed significant maximum LOD scores of 4.20(D14S990 and D14S264, sita = 0) in the family. Haplotype construction and multipoint linkage analysis also confirmed the locus and defined the isolated ADAAA locus to a 9.84 cM interval between the markers D14S283 and D14S297. Our study assigned an isolated ADAAA locus to 14q11.2–q12. This is the first ADAAA locus reported to date.Y. Yang and J. Guo contribute to this work equally. 相似文献
156.
Vascular endothelium in atherosclerosis 总被引:1,自引:0,他引:1
Their strategic location between blood and tissue and their constitutive properties allow endothelial cells (EC) to monitor
the transport of plasma molecules, by employing bidirectional receptor-mediated and receptor-independent transcytosis and
endocytosis, and to regulate vascular tone, cellular cholesterol and lipid homeostasis. These cells are also involved in signal
transduction, immunity, inflammation and haemostasis. Cardiovascular risk factors, such as hyperlipaemia/dyslipidaemia trigger
the molecular machinery of EC to respond to insults by modulation of their constitutive functions followed by dysfunction
and ultimately by injury and apoptosis. The gradual activation of EC consists initially in the modulation of two constitutive
functions: (1) permeability, i.e. increased transcytosis of lipoproteins, and (2) biosynthetic activity, i.e. enhanced synthesis
of the basement membrane and extracellular matrix. The increased transcytosis and the reduced efflux of β-lipoproteins (βLp)
lead to their retention within the endothelial hyperplasic basal lamina as modified lipoproteins (MLp) and to their subsequent
alteration (oxidation, glycation, enzymatic modifications). MLp generate chemoattractant and inflammatory molecules, triggering
EC dysfunction (appearance of new adhesion molecules, secretion of chemokines, cytokines), characterised by monocyte recruitment,
adhesion, diapedesis and residence within the subendothelium. In time, EC in the athero-prone areas alter their net negative
surface charge, losing their non-thrombogenic ability, become loaded with lipid droplets and turn into foam cells. Prolonged
and/or repeated exposure to cardiovascular risk factors can ultimately exhaust the protective effect of the endogenous anti-inflammatory
system within EC. As a consequence, EC may progress to senescence, lose their integrity and detach into the circulation. 相似文献
157.
Seyyed Javad Sabounchei Hassan Nemattalab Sima Khani Harry Adams 《Inorganica chimica acta》2009,362(1):105-2492
The reactions of phosphorus ylide (p-tolyl)3PCHC(O)CH3 (Y1) with HgX2 (X = Cl and Br) and (p-tolyl)3PCHC(O)C6H4NO2 (Y2) with HgX2 (X = Cl, Br and I) in equimolar ratios using methanol as a solvent are reported. These reactions led to binuclear complexes. C-Coordination of ylides and trans-like structure of complexes [(Y1) · HgBr2]2 and [(Y2) · HgBr2]2 · 2DMSO are demonstrated by single crystal X-ray analyses. The IR, 1H, 13C and 31P NMR data for the other synthesized compounds are similar to the latter complexes, indicating similar structures. Elemental analyses indicate a 1:1 stoichiometry between the ylide and Hg(II) halide in all the products. The ab initio studies indicated that for all dimeric compounds, the observed trans-like structures are 7-10 kcal/mol more stable than the alternative possible cis-like isomers. Although the calculated bond lengths are slightly longer than the measured ones, the similarity of calculated and measured bond angles reflects the similar geometrical structures for these compounds in both the solid state and the gas phase. 相似文献
158.
Cigang Yu Haidong Xu Guodong Huang Ting Chen Guiyou Liu Nan Chai Yin Ji Siyuan Wang Yijun Dai Sheng Yuan 《Applied microbiology and biotechnology》2010,86(3):863-870
The main product of the conversion of puerarin by unpermeabilized cells of bacterium Microbacterium oxydans CGMCC 1788 was puerarin-7-O-glucoside (241 ± 31.9 μM). Permeabilization with 40% ethanol could not increase conversion yield, whereas it resulted in
change of main product; a previous trace product became a main product (213 ± 48.0 μM) which was identified as a novel puerarin-7-O-fructoside by electrospray ionization time-of-flight MS, 13C NMR, 1H NMR, and GC-MS analysis of sugar composition, and puerarin-7-O-glucoside became a trace product (14.8 ± 5.4 μM). However, the extract from cells of M. oxydans CGMCC 1788 permeabilized with ethanol converted puerarin to form 113.9 ± 27.7 μM puerarin-7-O-glucoside and 187.8 ± 29.5 μM puerarin-7-O-fructoside under the same conditions. When unpermeabilized intact cells were recovered and used repeatedly for the conversion
of puerarin, with increase of reuse times, the yield of puerarin-7-O-glucoside gradually decreased, whereas the yield of puerarin-7-O-fructoside increased gradually in the conversion mixture. The main product of the conversion of puerarin by the tenth recycled
unpremerbilized cells was puerarin-7-O-fructoside (288.4 ± 24.0 μM). Therefore, the change of permeability of cell membrane of bacterium M. oxydans CGMCC 1788 contributed to the change of conversion of the product’s composition. 相似文献
159.
Rubin DL Lewis SE Mungall CJ Misra S Westerfield M Ashburner M Sim I Chute CG Solbrig H Storey MA Smith B Day-Richter J Noy NF Musen MA 《Omics : a journal of integrative biology》2006,10(2):185-198
The National Center for Biomedical Ontology is a consortium that comprises leading informaticians, biologists, clinicians, and ontologists, funded by the National Institutes of Health (NIH) Roadmap, to develop innovative technology and methods that allow scientists to record, manage, and disseminate biomedical information and knowledge in machine-processable form. The goals of the Center are (1) to help unify the divergent and isolated efforts in ontology development by promoting high quality open-source, standards-based tools to create, manage, and use ontologies, (2) to create new software tools so that scientists can use ontologies to annotate and analyze biomedical data, (3) to provide a national resource for the ongoing evaluation, integration, and evolution of biomedical ontologies and associated tools and theories in the context of driving biomedical projects (DBPs), and (4) to disseminate the tools and resources of the Center and to identify, evaluate, and communicate best practices of ontology development to the biomedical community. Through the research activities within the Center, collaborations with the DBPs, and interactions with the biomedical community, our goal is to help scientists to work more effectively in the e-science paradigm, enhancing experiment design, experiment execution, data analysis, information synthesis, hypothesis generation and testing, and understand human disease. 相似文献
160.