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排序方式: 共有75条查询结果,搜索用时 15 毫秒
1.
Protein kinase C in transmembrane signalling 总被引:8,自引:0,他引:8
2.
Peter J. Kavanagh Margaret E. Farago Iain Thornton Robert S. Braman 《Chemical Speciation and Bioavailability》2013,25(3):77-81
ABSTRACTThe southern part of the Tamar valley area in SW England is highly mineralised and mines in the region were the world's principal producers of tin, copper and arsenic during the mid nineteenth century. The Devon Great Consols Mine, covering 67.6 ha (167 acres) is situated in this area. Residues from the mining activity resulted in unvegetated spoil tips and local soils highly contaminated with As (range 120–52600 μg/g As). Sequential chemical extraction procedures were conducted on eight surface samples (0–15 cm) taken from a 2.0 km long transect from within the mine site to agricultural grassland. The proportion of water extractable As in agricultural top soils was lower (0.05–0.3%) than the values obtained for mine wastes (0.02–1.2%). Arsenic was found to be concentrated in the Fe-organic and residual fractions, which accounted for up 93 % of the total As in mine spoil and nearby soils. 相似文献
3.
Abstract Several different species of freshwater Bryozoa, belonging to the genera Plumatella, Rumarcanella and Fredericella, were detected within the Northern Mallee Pipeline (NMP) system in Victoria, Australia, that required definitive identification. These organisms produce asexual buds called statoblasts, with valves composed of sclerotised chitin that bear minute micro-ornamentations of considerable taxonomical significance. Imaging and analysis of these distinctive micro-ornamentations using scanning electron microscopy (SEM) is often employed for species identification. Meticulous preparation of statoblast samples is therefore required that necessitates the removal of adhering debris, dehydration and drying—whilst mitigating specimen damage and distortion. This technical note describes an approach whereby each of these three steps have been individually designed to be as benign as possible, using mild detergent/sonication to remove debris, a gradual and gentle dehydration procedure using ethanol, and critical point drying. For the overall process, these methods are chosen to optimise control and to minimise the use of harsh and hazardous chemicals. 相似文献
4.
5.
Salame MY More RS Verheye S Leimbach ME Iii SB Chronos NA 《International journal of cardiovascular interventions》1999,2(4):207-215
Glycoprotein IIb/IIIa receptor inhibitors represent a relatively new therapeutic approach in the field of antiplatelet therapy. Following the development of abciximab a number of small molecule GPIIb/IIIa inhibitors have been introduced such as tirofiban and eptifibatide. In this fast-moving field the interventional cardiologist needs a framework to guide decision-making for the individual patient. This review covers the efficacy and safety data from the clinical trials of GPIIb/IIIa inhibitors in the context of patients undergoing percutaneous coronary intervention for unstable angina/non-Q-wave myocardial infarction. There is an increasing body of evidence to support the efficacy of GPIIb/IIIa inhibitors in reducing the risk of adverse ischemic events in high and low risk patients undergoing percutaneous coronary intervention. A number of unresolved efficacy and safety issues remain, including the duration of treatment before and after intervention; whether a reduction in the heparin dose would further decrease the risk of hemorrhage without affecting the periprocedural thrombotic rate in patients undergoing PTCA with adjunctive GPIIb/IIIa inhibitors; and the cost-effectiveness of this therapy. When a thorough analysis of cost-effectiveness has been made, it will be easier to advocate the widespread use of these agents in all patients undergoing coronary intervention. 相似文献
6.
Beate-Annette Brüning Sylvain Prévost Ralf Stehle Roland Steitz Peter Falus Bela Farago Thomas Hellweg 《生物化学与生物物理学报:生物膜》2014
We report a combined dynamic light scattering (DLS) and neutron spin-echo (NSE) study on the local bilayer undulation dynamics of phospholipid vesicles composed of 1,2-dimyristoyl-glycero-3-phosphatidylcholine (DMPC) under the influence of temperature and the additives cholesterol and trehalose. The additives affect vesicle size and self-diffusion. Mechanical properties of the membrane and corresponding bilayer undulations are tuned by changing lipid headgroup or acyl chain properties through temperature or composition. On the local length scale, changes at the lipid headgroup influence the bilayer bending rigidity κ less than changes at the lipid acyl chain: We observe a bilayer softening around the main phase transition temperature Tm of the single lipid system, and stiffening when more cholesterol is added, in concordance with literature. Surprisingly, no effect on the mechanical properties of the vesicles is observed upon the addition of trehalose. 相似文献
7.
Michel Batista Fabricio K Marchini Paola AF Celedon Stenio P Fragoso Christian M Probst Henrique Preti Luiz S Ozaki Gregory A Buck Samuel Goldenberg Marco A Krieger 《BMC microbiology》2010,10(1):259
Background
The three trypanosomatids pathogenic to men, Trypanosoma cruzi, Trypanosoma brucei and Leishmania major, are etiological agents of Chagas disease, African sleeping sickness and cutaneous leishmaniasis, respectively. The complete sequencing of these trypanosomatid genomes represented a breakthrough in the understanding of these organisms. Genome sequencing is a step towards solving the parasite biology puzzle, as there are a high percentage of genes encoding proteins without functional annotation. Also, technical limitations in protein expression in heterologous systems reinforce the evident need for the development of a high-throughput reverse genetics platform. Ideally, such platform would lead to efficient cloning and compatibility with various approaches. Thus, we aimed to construct a highly efficient cloning platform compatible with plasmid vectors that are suitable for various approaches. 相似文献8.
Galit Lazer Liron Pe'er Marganit Farago Kazuya Machida Bruce J. Mayer Shulamit Katzav 《The Journal of biological chemistry》2010,285(30):23075-23085
The guanine nucleotide exchange factor (GEF) Vav1 is an essential signal transducer protein in the hematopoietic system, where it is expressed physiologically. It is also involved in several human malignancies. Tyrosine phosphorylation at the Vav1 amino terminus plays a central role in regulating its activity; however, the role of carboxyl terminal tyrosine residues is unknown. We found that mutation of either Tyr-826 (Y826F) or Tyr-841 (Y841F) to phenylalanine led to loss of Vav1 GEF activity. When these Vav1 mutants were ectopically expressed in pancreatic cancer cells lacking Vav1, they failed to induce growth in agar, indicating loss of transforming potential. Furthermore, although Y841F had no effect on Vav1-stimulated nuclear factor of activated T cells (NFAT) activity, Y826F doubled NFAT activity when compared with Vav1, suggesting that Tyr-826 mediates an autoinhibitory effect on NFAT activity. SH2 profiling revealed that Shc, Csk, Abl, and Sap associate with Tyr-826, whereas SH2-B, Src, Brk, GTPase-activating protein, and phospholipase C-γ associate with Tyr-841. Although the mutations in the Tyr-826 and Tyr-841 did not affect the binding of the carboxyl SH3 of Vav1 to other proteins, binding to several of the proteins identified by the SH2 profiling was lost. Of interest is Csk, which associates with wild-type Vav1 and Y841F, yet it fails to associate with Y826F, suggesting that loss of binding between Y826F and Csk might relieve an autoinhibitory effect, leading to increased NFAT. Our data indicate that GEF activity is critical for the function of Vav1 as a transforming protein but not for NFAT stimulation. The association of Vav1 with other proteins, detected by SH2 profiling, might affect other Vav1-dependent activities, such as NFAT stimulation. 相似文献
9.
Assembly of the brainstem cochlear nuclear complex is revealed by intersectional and subtractive genetic fate maps 总被引:5,自引:0,他引:5
The cochlear nuclear complex (CN) is the entry point for central auditory processing. Although constituent neurons have been studied physiologically, their embryological origins and molecular profiles remain obscure. Applying intersectional and subtractive genetic fate mapping approaches, we show that this complex develops modularly from genetically separable progenitor populations arrayed as rostrocaudal microdomains within and outside the hindbrain (lower) rhombic lip (LRL). The dorsal CN subdivision, structurally and topographically similar to the cerebellum, arises from microdomains unexpectedly caudal and noncontiguous to cerebellar primordium; ventral CN subdivisions arise from more rostral LRL. Magnocellular regions receive contributions from LRL and coaxial non-lip progenitors; contrastingly, ensheathing granule cells derive principally from LRL. Also LRL-derived and molecularly similar to CN granule cells are precerebellar mossy fiber neurons; surprisingly, these ostensibly intertwined populations have separable origins and adjacent but segregated migratory streams. Together, these findings provide new platforms for investigating the development and evolution of auditory and cerebellar systems. 相似文献
10.
Farago O Ewert K Ahmad A Evans HM Grønbech-Jensen N Safinya CR 《Biophysical journal》2008,95(2):836-846
Cationic lipids (CLs) have found widespread use as nonviral gene carriers (vectors), including applications in clinical trials of gene therapy. However, their observed transfection efficiencies (TEs) are inferior to those of viral vectors, providing a strong incentive for a detailed understanding of CL-DNA complex behavior. In recent systematic studies employing monovalent as well as newly synthesized multivalent lipids (MVLs), the membrane cationic charge density has been identified as a key parameter governing the TE of lamellar CL-DNA complexes. In this work, we use x-ray scattering and molecular simulations to investigate the structural properties of complexes containing MVLs. At low mole fraction of neutral lipids (NLs), ΦNL, the complexes show dramatic DNA compaction, down to essentially close-packed DNA arrays with a DNA interaxial spacing dDNA = 25 Å. A gradual increase in ΦNL does not lead to a continuous increase in dDNA as observed for DNA complexes of monovalent CLs. Instead, distinct spacing regimes exist, with sharp transitions between the regimes. Three packing states have been identified: 1), close packed, 2), condensed, but not close packed, with dDNA = 27-28 Å, and 3), an expanded state, where dDNA increases gradually with ΦNL. Based on our experimental and computational results, we conclude that the DNA condensation is mediated by the multivalent cationic lipids, which assemble between the negatively charged DNA rods. Quite remarkably, the computational results show that the less tightly packed structure in regime 2 is thermodynamically more stable than the close packed structure in regime 1. Accordingly, the constant DNA spacing observed in regime 2 is attributed to lateral phase coexistence between this stable CL-DNA complex and neutral membranes. This finding may explain the reduced TE measured for such complexes: transfection involves endosomal escape and disassembly of the complex, and these processes are inhibited by the high thermodynamic stability. Our results, which demonstrate the existence of an inverse correlation between the stability and transfection activity of lamellar CL-DNA complexes are, therefore, consistent with a recently proposed model of cellular entry. 相似文献