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121.
There is an often unspoken truth behind the course of scientific investigation that involves not what is necessarily academically worthy of study, but rather what is scientifically worthy in the eyes of funding agencies. The perception of worthy research is, as cost is driven in the simplest sense in economics, often driven by demand. Presently, the demand for novel diagnostic and therapeutic protein biomarkers that possess high sensitivity and specificity is placing major impact on the field of proteomics. The focal discovery technology that is being relied on is mass spectrometry (MS), whereas the challenge of biomarker discovery often lies not in the application of MS but in the underlying proteome sampling and bioinformatic processing strategies. Although biomarker discovery research has been historically technology-driven, it is clear from the meager success in generating validated biomarkers that increasing attention must be placed at the pre-analytic stage, such as sample retrieval and preparation. As diseases vary, so do the combinations of sampling and sample analyses necessary to discover novel biomarkers. In this review, we highlight different strategies used toward biomarker discovery and discuss them in terms of their reliance on technology and methodology. 相似文献
122.
红细胞在钙离子和离子载体A23187作用下的流变特性研究 总被引:1,自引:0,他引:1
用新激光衍射法研究了钙离子及离子载体A23187对红细胞流变特性的影响.用不同浓度的钙离子及离子载体A23187分别处理红细胞后,测量其取向指数和小变形指数.结果表明离子载体A23187较细胞外钙离子浓度对红细胞流变特性的影响更大.而且,最大取向指数和最大小变形指数随着钙离子及离子载体A23187浓度的增加而降低.离子载体A23187浓度增加导致红细胞变形能力明显降低. 相似文献
123.
不同退化阶段高寒草甸土壤化学计量特征 总被引:13,自引:1,他引:13
为了阐明不同退化阶段高寒草甸土壤的化学计量特征,沿着高寒草甸退化的梯度选取了原生嵩草草甸、轻度退化草甸和严重沙化草甸,测定了高寒草甸退化过程中不同深度土壤的有机碳、全氮、全磷和全钾含量。结果表明:随着高寒草甸的退化,0~100cm土壤的有机碳、全氮、全磷和全钾含量以及碳氮比、碳磷比、碳钾比、氮磷比、氮钾比和磷钾比均呈降低趋势,且土壤有机碳对高寒草甸退化的敏感性最高,全氮、全磷和全钾的敏感性依次降低,表层20cm的土壤有机碳和全氮可作为表征高寒草甸退化程度最敏感的土壤养分指标。另外,随着草甸的退化,土壤的有机碳、全氮、全磷和全钾含量及其化学计量比的垂直分布明显不同:随着土壤深度的增加,原生嵩草草甸和轻度退化草甸的土壤有机碳、全氮和全磷含量以及碳氮比、碳磷比、碳钾比、氮磷比、氮钾比和磷钾比在0~40cm范围内锐减,在40cm以下缓慢降低并趋于稳定;而沙化草甸土壤的有机碳、全氮、全磷和全钾及其化学计量比随着土壤深度的增加保持不变。 相似文献
124.
Proteomic and biochemical analysis of purified human immunodeficiency virus type 1 produced from infected monocyte-derived macrophages 总被引:6,自引:0,他引:6
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Chertova E Chertov O Coren LV Roser JD Trubey CM Bess JW Sowder RC Barsov E Hood BL Fisher RJ Nagashima K Conrads TP Veenstra TD Lifson JD Ott DE 《Journal of virology》2006,80(18):9039-9052
Human immunodeficiency virus type 1 (HIV-1) infects CD4(+) T lymphocytes and monocytes/macrophages, incorporating host proteins in the process of assembly and budding. Analysis of the host cell proteins incorporated into virions can provide insights into viral biology. We characterized proteins in highly purified HIV-1 virions produced from human monocyte-derived macrophages (MDM), within which virus buds predominantly into intracytoplasmic vesicles, in contrast to the plasmalemmal budding of HIV-1 typically seen with infected T cells. Liquid chromatography-linked tandem mass spectrometry of highly purified virions identified many cellular proteins, including 33 previously described proteins in HIV-1 preparations from other cell types. Proteins involved in many different cellular structures and functions were present, including those from the cytoskeleton, adhesion, signaling, intracellular trafficking, chaperone, metabolic, ubiquitin/proteasomal, and immune response systems. We also identified annexins, annexin-binding proteins, Rab proteins, and other proteins involved in membrane organization, vesicular trafficking, and late endosomal function, as well as apolipoprotein E, which participates in cholesterol transport, immunoregulation, and modulation of cell growth and differentiation. Several tetraspanins, markers of the late endosomal compartment, were also identified. MDM-derived HIV contained 26 of 37 proteins previously found in exosomes, consistent with the idea that HIV uses the late endosome/multivesicular body pathway during virion budding from macrophages. 相似文献
125.
Zusammenfassung An Hand von Mikrophotographien wird gezeigt, daß das Cytoplasma jeder Hornhautparenchymzelle von einer oder mehreren der netzförmig angeordneten feinsten Nervenfasern durchzogen wird. 相似文献
126.
David S. Gibson Joao Banha Deborah Penque Luciana Costa Thomas P. Conrads Dolores J. Cahill John K. O'Brien Madeleine E. Rooney 《Journal of Proteomics》2010,73(6):1045-1060
Current clinical, laboratory or radiological parameters cannot accurately diagnose or predict disease outcomes in a range of autoimmune disorders. Biomarkers which can diagnose at an earlier time point, predict outcome or help guide therapeutic strategies in autoimmune diseases could improve clinical management of this broad group of debilitating disorders. Additionally, there is a growing need for a deeper understanding of multi-factorial autoimmune disorders.Proteomic platforms offering a multiplex approach are more likely to reflect the complexity of autoimmune disease processes. Findings from proteomic based studies of three distinct autoimmune diseases are presented and strategies compared. It is the authors' view that such approaches are likely to be fruitful in the movement of autoimmune disease treatment away from reactive decisions and towards a preventative stand point. 相似文献
127.
KA Hyndman DH Evans 《Comparative biochemistry and physiology. Part A, Molecular & integrative physiology》2009,152(1):58-65
We recently determined that rapid changes in environmental salinity alter endothelin-1 (EDN1) mRNA levels in the euryhaline killifish, Fundulus heteroclitus, so we hypothesized that EDN1 may be a local regulator of gill ion transport in teleost fishes. The purpose of the present study was to examine the effects of changes in environmental salinity on the gill endothelin receptors: EDNRA, EDNRB, and EDNRC. Using quantitative real-time PCR, we determined that after a fresh water (FW) to seawater (SW) transfer, there is a two to threefold increase in gill EDNRA and EDNRB mRNA levels. Likewise, we found a two to three fold increase in gill EDNRA and EDNRB protein concentration. In addition, killifish that have acclimated to FW for 30 days had significantly lower EDNRA mRNA and protein levels than SW killifish. ENDRA were immunolocalized to the mitochondrion-rich cells of the killifish gill, suggesting that EDN1 signaling cascades may affect MRC function. EDNRB were found throughout the gill vasculature and on lamellar pillar cells. We previously immunolocalized EDN1 to the pillar cell suggesting that EDN1 acts as an autocrine signaling molecule and potentially regulates pillar cell tone and lamellar perfusion. We conclude that EDN1 is physiologically active in the teleost gill, and regulated by environmental salinity. Future functional studies examining the physiological role of this system are necessary to completely understand EDN1 in the fish gill. 相似文献
128.
Jayaraman T Tejero J Chen BB Blood AB Frizzell S Shapiro C Tiso M Hood BL Wang X Zhao X Conrads TP Mallampalli RK Gladwin MT 《The Journal of biological chemistry》2011,286(49):42679-42689
Neuroglobin protects neurons from hypoxia in vitro and in vivo; however, the underlying mechanisms for this effect remain poorly understood. Most of the neuroglobin is present in a hexacoordinate state with proximal and distal histidines in the heme pocket directly bound to the heme iron. At equilibrium, the concentration of the five-coordinate neuroglobin remains very low (0.1-5%). Recent studies have shown that post-translational redox regulation of neuroglobin surface thiol disulfide formation increases the open probability of the heme pocket and allows nitrite binding and reaction to form NO. We hypothesized that the equilibrium between the six- and five-coordinate states and secondary reactions with nitrite to form NO could be regulated by other hypoxia-dependent post-translational modification(s). Protein sequence models identified candidate sites for both 14-3-3 binding and phosphorylation. In both in vitro experiments and human SH-SY5Y neuronal cells exposed to hypoxia and glucose deprivation, we observed that 1) neuroglobin phosphorylation and protein-protein interactions with 14-3-3 increase during hypoxic and metabolic stress; 2) neuroglobin binding to 14-3-3 stabilizes and increases the half-life of phosphorylation; and 3) phosphorylation increases the open probability of the heme pocket, which increases ligand binding (CO and nitrite) and accelerates the rate of anaerobic nitrite reduction to form NO. These data reveal a series of hypoxia-dependent post-translational modifications to neuroglobin that regulate the six-to-five heme pocket equilibrium and heme access to ligands. Hypoxia-regulated reactions of nitrite and neuroglobin may contribute to the cellular adaptation to hypoxia. 相似文献
129.
130.
Lennart KA Lundblad Lisa M Rinaldi Matthew E Poynter Erik P Riesenfeld Min Wu Steven Aimi Leesa M Barone Jason HT Bates Charles G Irvin 《Respiratory research》2011,12(1):27