全文获取类型
收费全文 | 462篇 |
免费 | 24篇 |
专业分类
486篇 |
出版年
2023年 | 2篇 |
2022年 | 2篇 |
2021年 | 10篇 |
2020年 | 6篇 |
2019年 | 7篇 |
2018年 | 4篇 |
2017年 | 6篇 |
2016年 | 15篇 |
2015年 | 20篇 |
2014年 | 25篇 |
2013年 | 33篇 |
2012年 | 29篇 |
2011年 | 36篇 |
2010年 | 14篇 |
2009年 | 20篇 |
2008年 | 34篇 |
2007年 | 43篇 |
2006年 | 20篇 |
2005年 | 14篇 |
2004年 | 22篇 |
2003年 | 16篇 |
2002年 | 23篇 |
2001年 | 6篇 |
2000年 | 2篇 |
1999年 | 4篇 |
1998年 | 2篇 |
1997年 | 3篇 |
1996年 | 2篇 |
1995年 | 2篇 |
1994年 | 3篇 |
1993年 | 3篇 |
1992年 | 4篇 |
1991年 | 8篇 |
1989年 | 1篇 |
1988年 | 5篇 |
1987年 | 2篇 |
1985年 | 2篇 |
1984年 | 2篇 |
1983年 | 4篇 |
1982年 | 4篇 |
1981年 | 10篇 |
1980年 | 3篇 |
1979年 | 2篇 |
1978年 | 3篇 |
1975年 | 1篇 |
1974年 | 3篇 |
1964年 | 1篇 |
1960年 | 2篇 |
1959年 | 1篇 |
排序方式: 共有486条查询结果,搜索用时 12 毫秒
31.
Zoltan Mastala Sndor Herodek Katalin V.-Balogh Gyrgy Borbly Hesham Mohamed Shafik Lajos Vrs 《International Review of Hydrobiology》1996,81(4):503-512
A pico sized Synechococcus species isolated from Lake Balaton was studied in batch and continuous cultures. This picocyanobacterium had a pH optimum at 8.5 and a temperature optimum at 28-30°C. The Ik value for growth was 52 μEinstein m−2 S−1, the maximum growth rate 2.27 d−1, the half saturation Constant of growth 1.2 μg PO4-P I−1 and the minimal cell quota 1.74 nig P g dry weight−1. The dry weight of cells showed a minimum, the chlorophyll-a/biomass ratio a maximum as a function of growth rate. Above the quota of 3.4 fg P Cell−1 significant amounts of non-reactive dissolved Phosphorous were released. 相似文献
32.
Single cell lineage and regionalization of cell populations during Medaka neurulation 总被引:2,自引:0,他引:2
Hirose Y Varga ZM Kondoh H Furutani-Seiki M 《Development (Cambridge, England)》2004,131(11):2553-2563
To study the movement of individual cells and development of cell grouping during neurogenesis, we labeled single cells in early Medaka gastrula at stage 13 [13 hours post-fertilization (hpf)] with a fluorescent vital dye, and analyzed cells and their descendants using time-lapse live recording up to stage 24 (44 hpf). At stage 13, all future neural cells were located in a dorsal 140 degrees sector of the embryo, and migrated toward the vegetal pole; but during stage 15 to 16, they converged towards the midline. Cells that contributed to later neural subdivisions initially formed overlapping populations, but after stage 16+ they formed non-overlapping cell groups having characteristics of tissue 'compartments', preceding development of morphologically distinct neural subdivisions. In early retinal development, a single compartment for future retinal cells was formed superficial to telencephalic and diencephalic compartments, but it was split into left and right eye components at stage 17 in parallel with anterodorsal movement of the diencephalic compartment. At stage 16+, when these compartments were established, Pax6 expression initiated, but only in the laterally located subpopulation of the retina precursor. These observations revise the current view of bilateral retinal development. Continuous live recording of labeled single precursor cells and computer graphics-assisted data analysis, which are presented for the first time in this study, provide excellent means with which to analyze essential cellular processes in organogenesis. 相似文献
33.
34.
Mak S Egri Z Tanna G Colman R Newton GE 《American journal of physiology. Heart and circulatory physiology》2002,282(6):H2414-H2421
High arterial blood oxygen tension increases vascular resistance, possibly related to an interaction between reactive oxygen species and endothelium-derived vasoactive factors. Vitamin C is a potent antioxidant capable of reversing endothelial dysfunction due to increased oxidant stress. We tested the hypotheses that hyperoxic vasoconstriction would be prevented by vitamin C, and that acetylcholine-mediated vasodilation would be blunted by hyperoxia and restored by vitamin C. Venous occlusion strain gauge plethysmography was used to measure forearm blood flow (FBF) in 11 healthy subjects and 15 congestive heart failure (CHF) patients, a population characterized by endothelial dysfunction and oxidative stress. The effect of hyperoxia on FBF and derived forearm vascular resistance (FVR) at rest and in response to intra-arterial acetylcholine was recorded. In both healthy subjects and CHF patients, hyperoxia-mediated increases in basal FVR were prevented by the coinfusion of vitamin C. In healthy subjects, hyperoxia impaired the acetylcholine-mediated increase in FBF, an effect also prevented by vitamin C. In contrast, hyperoxia had no effect on verapamil-mediated increases in FBF. In CHF patients, hyperoxia did not affect FBF responses to acetylcholine or verapamil. The addition of vitamin C during hyperoxia augmented FBF responses to acetylcholine. These results suggest that hyperoxic vasoconstriction is mediated by oxidative stress. Moreover, hyperoxia impairs acetylcholine-mediated vasodilation in the setting of intact endothelial function. These effects of hyperoxia are prevented by vitamin C, providing evidence that hyperoxia-derived free radicals impair the activity of endothelium-derived vasoactive factors. 相似文献
35.
A membrane oxidation assay is presented which uses isolated erythrocyte membranes ("ghosts") and lipoxygenase as a selective catalyst for the transfer of oxygen to cis - cis -1,4-pentadiene-moieties. The latter are, for instance, present in linoleic and arachidonic acids, both of which are integral parts of membranes. These non-conjugated double bonds represent energetically favorable sites for oxidative attack and therefore, may be rearranged and partially consumed during oxidative stress. Consequently, the measurement of oxygen consumption in the course of the lipoxygenase-mediated oxidation provides a tool for the quick and reliable determination of such double bonds. Significant inter-individual differences have been noted in 11 subjects, which also correlate to the total radical antioxidant parameter (TRAP) values obtained. This assay will be helpful in the assessment of oxidizable structures in erythrocyte membranes that may be diminished as a consequence of oxidative damage suffered by an individual. In conclusion, a simple and rapid assay for the assessment of the oxidizability of erythrocyte membranes is presented complementing the TRAP assay for plasma antioxidative status. 相似文献
36.
Annina Kelloniemi Zoltan Szabo Raisa Serpi Juha N?p?nkangas Pauli Ohukainen Olli Tenhunen Leena Kaikkonen Elina Koivisto Zsolt Bagyura Risto Kerkel? Margret Leosdottir Thomas Hedner Olle Melander Heikki Ruskoaho Jaana Rys? 《PloS one》2015,10(6)
The phosphatase and actin regulator 1 (PHACTR1) locus is a very commonly identified hit in genome-wide association studies investigating coronary artery disease and myocardial infarction (MI). However, the function of PHACTR1 in the heart is still unknown. We characterized the mechanisms regulating Phactr1 expression in the heart, used adenoviral gene delivery to investigate the effects of Phactr1 on cardiac function, and analyzed the relationship between MI associated PHACTR1 allele and cardiac function in human subjects. Phactr1 mRNA and protein levels were markedly reduced (60%, P<0.01 and 90%, P<0.001, respectively) at 1 day after MI in rats. When the direct myocardial effects of Phactr1 were studied, the skeletal α-actin to cardiac α-actin isoform ratio was significantly higher (1.5-fold, P<0.05) at 3 days but 40% lower (P<0.05) at 2 weeks after adenovirus-mediated Phactr1 gene delivery into the anterior wall of the left ventricle. Similarly, the skeletal α-actin to cardiac α-actin ratio was lower at 2 weeks in infarcted hearts overexpressing Phactr1. In cultured neonatal cardiac myocytes, adenovirus-mediated Phactr1 overexpression for 48 hours markedly increased the skeletal α-actin to cardiac α-actin ratio, this being associated with an enhanced DNA binding activity of serum response factor. Phactr1 overexpression exerted no major effects on the expression of other cardiac genes or LV structure and function in normal and infarcted hearts during 2 weeks’ follow-up period. In human subjects, MI associated PHACTR1 allele was not associated significantly with cardiac function (n = 1550). Phactr1 seems to regulate the skeletal to cardiac α-actin isoform ratio. 相似文献
37.
Influence of HDL-cholesterol-elevating drugs on the in vitro activity of the HDL receptor SR-BI 总被引:1,自引:0,他引:1
Nieland TJ Shaw JT Jaipuri FA Maliga Z Duffner JL Koehler AN Krieger M 《Journal of lipid research》2007,48(8):1832-1845
Treatment of atherosclerotic disease often focuses on reducing plasma LDL-cholesterol or increasing plasma HDL-cholesterol. We examined in vitro the effects on HDL receptor [scavenger receptor class B type I (SR-BI)] activity of three classes of clinical and experimental plasma HDL-cholesterol-elevating compounds: niacin, fibrates, and HDL376. Fenofibrate (FF) and HDL376 were potent (IC(50) approximately 1 microM), direct inhibitors of SR-BI-mediated lipid transport in cells and in liposomes reconstituted with purified SR-BI. FF, a prodrug, was a more potent inhibitor of SR-BI than an activator of peroxisome proliferator-activated receptor alpha, a target of its active fenofibric acid (FFA) derivative. Nevertheless, FFA, four other fibrates (clofibrate, gemfibrozil, ciprofibrate, and bezafibrate), and niacin had little, if any, effect on SR-BI, suggesting that they do not directly target SR-BI in vivo. However, similarities of HDL376 treatment and SR-BI gene knockout on HDL metabolism in vivo (increased HDL-cholesterol and HDL particle sizes) and structure-activity relationship analysis suggest that SR-BI may be a target of HDL376 in vivo. HDL376 and other inhibitors may help elucidate SR-BI function in diverse mammalian models and determine the therapeutic potential of SR-BI-directed pharmaceuticals. 相似文献
38.
Monoclonal antibodies to phosphatidylinositol phosphate neutralize human immunodeficiency virus type 1: role of phosphate-binding subsites 总被引:1,自引:0,他引:1
下载免费PDF全文
![点击此处可从《Journal of virology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Brown BK Karasavvas N Beck Z Matyas GR Birx DL Polonis VR Alving CR 《Journal of virology》2007,81(4):2087-2091
Both a murine monoclonal antibody to phosphatidylinositol phosphate (PIP) and a human monoclonal antibody (4E10) that is known to have broadly neutralizing capabilities against primary isolates of human immunodeficiency virus type 1 (HIV-1) bound to PIP, as determined by enzyme-linked immunosorbent assay. Each of the antibodies had antigen subsite binding specificities in aqueous medium for small phosphate-containing molecules and for inositol. The anti-PIP monoclonal antibody inhibited infection by two HIV-1 primary isolates in neutralization assays employing primary human peripheral blood mononuclear cells. The data suggest that PIP or related lipids having free phosphates could serve as targets for the neutralization of HIV-1. 相似文献
39.
Dual effect of acid pH on purinergic P2X3 receptors depends on the histidine 206 residue 总被引:1,自引:0,他引:1
Gerevich Z Zadori ZS Köles L Kopp L Milius D Wirkner K Gyires K Illes P 《The Journal of biological chemistry》2007,282(47):33949-33957
Whole cell patch clamp investigations were carried out to clarify the pH sensitivity of native and recombinant P2X(3) receptors. In HEK293 cells permanently transfected with human (h) P2X(3) receptors (HEK293-hP2X(3) cells), an acidic pH shifted the concentration-response curve for alpha,beta-methylene ATP (alpha,beta-meATP) to the right and increased its maximum. An alkalic pH did not alter the effect of alpha,beta-meATP. Further, a low pH value increased the activation time constant (tau(on)) of the alpha,beta-meATP current; the fast and slow time constants of desensitization (tau(des1), tau(des2)) were at the same time also increased. Finally, acidification accelerated the recovery of P2X(3) receptors from the desensitized state. Replacement of histidine 206, but not histidine 45, by alanine abolished the pH-induced effects on hP2X(3) receptors transiently expressed in HEK293 cells. Changes in the intracellular pH had no effect on the amplitude or time course of the alpha,beta-meATP currents. The voltage sensitivity and reversal potential of the currents activated by alpha,beta-meATP were unaffected by extracellular acidification. Similar effects were observed in a subpopulation of rat dorsal root ganglion neurons expressing homomeric P2X(3) receptor channels. It is suggested that acidification may have a dual effect on P2X(3) channels, by decreasing the current amplitude at low agonist concentrations (because of a decrease in the rate of activation) and increasing it at high concentrations (because of a decrease in the rate of desensitization). Thereby, a differential regulation of pain sensation during e.g. inflammation may occur at the C fiber terminals of small DRG neurons in peripheral tissues. 相似文献
40.
IgG opsonization of HIV impedes provirus formation in and infection of dendritic cells and subsequent long-term transfer to T cells 总被引:3,自引:0,他引:3
Wilflingseder D Banki Z Garcia E Pruenster M Pfister G Muellauer B Nikolic DS Gassner C Ammann CG Dierich MP Piguet V Stoiber H 《Journal of immunology (Baltimore, Md. : 1950)》2007,178(12):7840-7848
Already at initial phases of infection, HIV is coated with complement fragments. During the chronic phase, when HIV-specific IgGs appear, the virus circulates immune complexed with IgG and complement. Thus, we studied the interaction of dendritic cells (DCs) and DC-T cell cocultures with complement (C)-opsonized and C-IgG-opsonized HIV. HIV infection of monocyte-derived DCs and circulating BDCA-1-positive DCs was significantly reduced upon the presence of virus-specific but non-neutralizing IgGs. DCs exposed to C-Ig-HIV or IgG-opsonized HIV showed an impaired provirus formation and p24 production and a decreased transmission rate to autologous nonstimulated T cells upon migration along a chemokine gradient. This reduced infectivity was also observed in long-term experiments, when T cells were added delayed to DCs exposed to IgG-coated HIV without migration. Similar kinetics were seen when sera from HIV-1-infected individuals before and after seroconversion were used in infection assays. Both C- and C-IgG-opsonized HIV were captured and targeted to a tetraspanin-rich endosome in immature DCs, but differed with respect to MHC class II colocalization. The reduced infection by IgG-opsonized HIV is possibly due to interactions of virus-bound IgG with FcgammaRIIb expressed on DCs. Therefore, the intracellular fate and transmission of immune-complexed HIV seems to differ depending on time and opsonization pattern. 相似文献