全文获取类型
收费全文 | 167篇 |
免费 | 12篇 |
出版年
2021年 | 2篇 |
2020年 | 5篇 |
2019年 | 4篇 |
2018年 | 5篇 |
2017年 | 3篇 |
2016年 | 9篇 |
2015年 | 8篇 |
2014年 | 9篇 |
2013年 | 12篇 |
2012年 | 13篇 |
2011年 | 17篇 |
2010年 | 15篇 |
2009年 | 12篇 |
2008年 | 11篇 |
2007年 | 9篇 |
2006年 | 8篇 |
2005年 | 6篇 |
2004年 | 6篇 |
2003年 | 2篇 |
2002年 | 4篇 |
2001年 | 4篇 |
2000年 | 2篇 |
1999年 | 3篇 |
1998年 | 2篇 |
1995年 | 1篇 |
1994年 | 1篇 |
1992年 | 1篇 |
1988年 | 1篇 |
1979年 | 1篇 |
1974年 | 1篇 |
1969年 | 1篇 |
1947年 | 1篇 |
排序方式: 共有179条查询结果,搜索用时 78 毫秒
41.
Jens-Uwe Peters Holger Kühne Henrietta Dehmlow Uwe Grether Aurelia Conte Dominik Hainzl Cornelia Hertel Nicole A. Kratochwil Michael Otteneder Robert Narquizian Constantinos G. Panousis Fabienne Ricklin Stephan Röver 《Bioorganic & medicinal chemistry letters》2010,20(18):5426-5430
Pyrido pyrimidinones are selective agonists of the human high affinity niacin receptor GPR109A (HM74A). They show no activity on the highly homologous low affinity receptor GPR109B (HM74). Starting from a high throughput screening hit the in vitro activity of the pyrido pyrimidinones was significantly improved providing lead compounds suitable for further optimization. 相似文献
42.
Campanacci V Dubois DY Becker HD Kern D Spinelli S Valencia C Pagot F Salomoni A Grisel S Vincentelli R Bignon C Lapointe J Giegé R Cambillau C 《Journal of molecular biology》2004,337(2):273-283
In the course of a structural genomics program aiming at solving the structures of Escherichia coli open reading frame products of unknown function, we have determined the structure of YadB at 1.5A using molecular replacement. The YadB protein is 298 amino acid residues long and displays 34% sequence identity with E.coli glutamyl-tRNA synthetase (GluRS). It is much shorter than GluRS, which contains 468 residues, and lacks the complete domain interacting with the tRNA anticodon loop. As E.coli GluRS, YadB possesses a Zn2+ located in the putative tRNA acceptor stem-binding domain. The YadB cluster uses cysteine residues as the first three zinc ligands, but has a weaker tyrosine ligand at the fourth position. It shares with canonical amino acid RNA synthetases a major functional feature, namely activation of the amino acid (here glutamate). It differs, however, from GluRSs by the fact that the activation step is tRNA-independent and that it does not catalyze attachment of the activated glutamate to E.coli tRNAGlu, but to another, as yet unknown tRNA. These results suggest thus a novel function, distinct from that of GluRSs, for the yadB gene family. 相似文献
43.
Roberto de Marco Francesca Locatelli Lucia Cazzoletti Massimilian Bugianio Aurelia Carosso Alessandra Marinoni 《Respiratory research》2005,6(1):1-10
Background
CpG-oligonucleotides (CpG-ODN), which induce signaling through Toll-like receptor 9 (TLR9), are currently under investigation as adjuvants in therapy against infections and cancer. CpG-ODN function as Th-1 adjuvants and are able to activate dendritic cells. In humans TLR9 has been described to be strongly expressed in B-lymphocytes, monocytes, plasmacytoid dendritic cells and at low levels in human respiratory cells. We determined whether a direct interaction of bacterial DNA with the tumor cells themselves is possible and investigated the expression and function of TLR9 in human malignant solid tumors and cell lines. TLR9 expression by malignant tumor cells, would affect treatment approaches using CpG-ODN on the one hand, and, on the other hand, provide additional novel information about the role of tumor cells in tumor-immunology.Methods
The expression of TLR9 in HOPE-fixed non-small lung cancer, non-malignant tissue and tumor cell lines was assessed using immunohistochemistry, confocal microscopy, in situ hybridization, RT-PCR and DNA-sequencing. Apoptosis and chemokine expression was detected by FACS analysis and the Bio-Plex system.Results
We found high TLR9 signal intensities in the cytoplasm of tumor cells in the majority of lung cancer specimens as well as in all tested tumor cell lines. In contrast to this non-malignant lung tissues showed only sporadically weak expression. Stimulation of HeLa and A549 cells with CpG-ODN induced secretion of monocyte chemoattractant protein-1 and reduction of spontaneous and tumor necrosis factor-alpha induced apoptosis.Conclusions
Here we show that TLR9 is expressed in a selection of human lung cancer tissues and various tumor cell lines. The expression of functionally active TLR9 in human malignant tumors might affect treatment approaches using CpG-ODN and shows that malignant cells can be regarded as active players in tumor-immunology. 相似文献44.
Fattorossi A Battaglia A Pierelli L Malinconico P Andreocci L Perillo A Ferrandina G Martelli O Rughetti A Nuti M Cortesi E Scambia G 《Cancer immunology, immunotherapy : CII》2001,49(12):641-648
Thirty-four ovarian and breast cancer patients received autologous peripheral blood progenitor cell transplantation after high-dose myeloablative chemotherapy and either granulocyte-colony-stimulating factor (G-CSF) or granulocyte/macrophage-colony-stimulating fictor (GM-CSF) in the immediate post-transplant period. The recovery of T cell functionality was monitored by a three-color flow-cytometric approach using carboxyfluorescein diacetate succinimidyl ester, a probe the fluorescence intensity of which halves at each round of cell replication, in conjunction with CD3 and CD25 monoclonal antibodies. There was no significant difference between the two treatments on days 12, 20, and 40, T cell proliferation always being considerably lower than that of control cultures from healthy donors. At day 80, a significantly higher proportion of mitogen-stimulated T cells from GM-CSF-treated patients expressed interleukin-2 receptor, and a higher proportion of these T cells were actively proliferating. This phenomenon did not reflect any difference in the relative proportion of various lymphocyte subsets (T cells, CD4 and CD8+ T cells, CD45RA+ and CD45RO- T cells, and natural killer cells). At the end of follow-up (1-1.5 years) T cell proliferation had returned to values typically observed in healthy individuals in both groups of patients. Soon after transplantation (day 12), neutrophils from G-CSF-treated patients had a more elevated Fcgamma receptor I density and monocytes from GM-CSF-treated patients had a more elevated Fcgamma receptor II and MHC class II molecules density. The up-modulation of Fcgamma receptor II was maintained until day 40. Thus, administering G-CSF and GM-CSF in the post-transplant period affects T lymphocyte proliferation and phagocyte membrane molecules differently. 相似文献
45.
Altemar S Paigel Rogerio F Ribeiro Junior Aurelia A Fernandes Gabriel P Targueta Dalton V Vassallo Ivanita Stefanon 《Reproductive biology and endocrinology : RB&E》2011,9(1):54
Background
Ovarian sex hormones (OSHs) are implicated in cardiovascular function. It has been shown that OSHs play an important role in the long term regulation of cardiac sarcoplasmic reticulum (SR) function and contractility, although early effects of OSHs deprivation on myocardial contractility have not yet been determined. This study evaluated the early and late effects of OSHs deficiency on left ventricular contractility in rats after ovariectomy. 相似文献46.
Achilli A Olivieri A Pala M Hooshiar Kashani B Carossa V Perego UA Gandini F Santoro A Battaglia V Grugni V Lancioni H Sirolla C Bonfigli AR Cormio A Boemi M Testa I Semino O Ceriello A Spazzafumo L Gadaleta MN Marra M Testa R Franceschi C Torroni A 《PloS one》2011,6(6):e21029
Mitochondrial dysfunction has been implicated in rare and common forms of type 2 diabetes (T2DM). Additionally, rare mitochondrial DNA (mtDNA) mutations have been shown to be causal for T2DM pathogenesis. So far, many studies have investigated the possibility that mtDNA variation might affect the risk of T2DM, however, when found, haplogroup association has been rarely replicated, even in related populations, possibly due to an inadequate level of haplogroup resolution. Effects of mtDNA variation on diabetes complications have also been proposed. However, additional studies evaluating the mitochondrial role on both T2DM and related complications are badly needed. To test the hypothesis of a mitochondrial genome effect on diabetes and its complications, we genotyped the mtDNAs of 466 T2DM patients and 438 controls from a regional population of central Italy (Marche). Based on the most updated mtDNA phylogeny, all 904 samples were classified into 57 different mitochondrial sub-haplogroups, thus reaching an unprecedented level of resolution. We then evaluated whether the susceptibility of developing T2DM or its complications differed among the identified haplogroups, considering also the potential effects of phenotypical and clinical variables. MtDNA backgrounds, even when based on a refined haplogroup classification, do not appear to play a role in developing T2DM despite a possible protective effect for the common European haplogroup H1, which harbors the G3010A transition in the MTRNR2 gene. In contrast, our data indicate that different mitochondrial haplogroups are significantly associated with an increased risk of specific diabetes complications: H (the most frequent European haplogroup) with retinopathy, H3 with neuropathy, U3 with nephropathy, and V with renal failure. 相似文献
47.
Jiabin Qi Shuo Chen Chuntao Lan Aurelia Chi Wang Xun Cui Zhengwei You Qinghong Zhang Yaogang Li Zhong Lin Wang Hongzhi Wang Zhiqun Lin 《Liver Transplantation》2020,10(35)
Increasing performance demand associated with the short lifetime of consumer electronics has triggered fast growth in electronic waste, leading to serious ecological challenges worldwide. Herein, a robust strategy for judiciously constructing flexible perovskite solar cells (PSCs) that can be conveniently biodegraded is reported. The key to this strategy is to capitalize on meniscus‐assisted solution printing (MASP) as a facile means of yielding cross‐aligned silver nanowires in one‐step, which are subsequently impregnated in a biodegradable elastomeric polyester. Intriguingly, the as‐crafted hybrid biodegradable electrode greatly constrains the solvent evaporation of the perovskite precursor solution, thereby generating fewer nuclei and in turn resulting in the deposition of a large‐grained dense perovskite film that exhibits excellent optoelectronic properties with a power conversion efficiency of 17.51% in PSCs. More importantly, the hybrid biodegradable electrode‐based devices also manifest impressive robustness against mechanical deformation and can be thoroughly biodegraded after use. These results signify the great potential of MASP for controllably assembling aligned conductive nanomaterials for biodegradable electrodes. As such, it represents an important endeavor toward environmentally friendly, multifunctional and flexible electronic, optoelectronic, photonic, and sensory materials and devices. 相似文献
48.
49.
Giorgio Honsell Alois Bonifacio Marco De Bortoli Antonella Penna Cecilia Battocchi Patrizia Ciminiello Carmela Dell’Aversano Ernesto Fattorusso Silvio Sosa Takeshi Yasumoto Aurelia Tubaro 《PloS one》2013,8(2)
The harmful dinoflagellate Ostreopsis cf. ovata has been causing toxic events along the Mediterranean coasts and other temperate and tropical areas, with increasing frequency during the last decade. Despite many studies, important biological features of this species are still poorly known. An integrated study, using different microscopy and molecular techniques, Raman microspectroscopy and high resolution liquid chromatography-mass spectrometry (HR LC-MS), was undertaken to elucidate cytological aspects, and identify main metabolites including toxins. The species was genetically identified as O. cf. ovata, Atlantic-Mediterranean clade. The ultrastructural results show unique features of the mucilage network abundantly produced by this species to colonize benthic substrates, with a new role of trichocysts, never described before. The amorphous polysaccharidic component of mucilage appears to derive from pusule fibrous material and mucocysts. In all stages of growth, the cells show an abundant production of lipids. Different developmental stages of chloroplasts are found in the peripheral cytoplasm and in the centre of cell. In vivo Raman microspectroscopy confirms the presence of the carotenoid peridinin in O. cf. ovata, and detects in several specimen the abundant presence of unsaturated lipids structurally related to docosahexaenoic acid. The HR LC-MS analysis reveals that ovatoxin-a is the predominant toxin, together with decreasing amounts of ovatoxin-b, -d/e, -c and putative palytoxin. Toxins concentration on a per cell basis increases from exponential to senescent phase. The results suggest that benthic blooms of this species are probably related to features such as the ability to create a unique mucilaginous sheath covering the sea bottom, associated with the production of potent toxins as palytoxin-like compounds. In this way, O. cf. ovata may be able to rapidly colonize benthic substrates outcompeting other species. 相似文献
50.
Tarja Oksanen Lauri Oksanen Katariina E. M. Vuorinen Christopher Wolf Aurelia Mäkynen Johan Olofsson William J. Ripple Risto Virtanen Tove Aa. Utsi 《Ecography》2020,43(12):1859-1877
Many terrestrial endotherm food webs constitute three trophic level cascades. Others have two trophic level dynamics (food limited herbivores; plants adapted to tackle intense herbivory) or one trophic level dynamic (herbivorous endotherms absent, thus plants compete for the few places where they can survive and grow). According to the Exploitation Ecosystems Hypothesis (EEH), these contrasting dynamics are consequences of differences in primary productivity. The productivity thresholds for changing food web dynamics were assumed to be global constants. We challenged this assumption and found that several model parameters are sensitive to the contrast between persistently warm and seasonally cold climates. In persistently warm environments, three trophic level dynamics can be expected to prevail almost everywhere, save the most extreme deserts. We revised EEH accordingly and tested it by compiling direct evidence of three and two trophic level dynamics and by studying the global distribution of felids. In seasonally cold environments, we found evidence for three trophic level dynamics only in productive ecosystems, while evidence for two trophic level dynamics appeared in ecosystems with low primary productivity. In persistently warm environments, we found evidence for three trophic level dynamics in all types of ecosystems. The distribution of felids corroborated these results. The empirical evidence thus indicates that two trophic level dynamics, as defined by EEH, are restricted to seasonally cold biomes with low primary productivity, such as the artic–alpine tundra and the temperate steppe. 相似文献