全文获取类型
收费全文 | 305篇 |
免费 | 29篇 |
专业分类
334篇 |
出版年
2023年 | 2篇 |
2021年 | 5篇 |
2020年 | 5篇 |
2019年 | 3篇 |
2018年 | 4篇 |
2017年 | 5篇 |
2016年 | 4篇 |
2015年 | 16篇 |
2014年 | 9篇 |
2013年 | 15篇 |
2012年 | 12篇 |
2011年 | 16篇 |
2010年 | 12篇 |
2009年 | 12篇 |
2008年 | 13篇 |
2007年 | 12篇 |
2006年 | 13篇 |
2005年 | 4篇 |
2004年 | 6篇 |
2003年 | 5篇 |
2002年 | 8篇 |
2001年 | 11篇 |
2000年 | 3篇 |
1999年 | 13篇 |
1998年 | 15篇 |
1997年 | 6篇 |
1996年 | 10篇 |
1995年 | 7篇 |
1994年 | 4篇 |
1993年 | 6篇 |
1992年 | 2篇 |
1991年 | 9篇 |
1990年 | 5篇 |
1989年 | 4篇 |
1988年 | 5篇 |
1987年 | 7篇 |
1986年 | 4篇 |
1985年 | 7篇 |
1984年 | 2篇 |
1983年 | 2篇 |
1982年 | 2篇 |
1981年 | 4篇 |
1980年 | 3篇 |
1979年 | 3篇 |
1978年 | 3篇 |
1977年 | 5篇 |
1975年 | 3篇 |
1974年 | 2篇 |
1968年 | 1篇 |
1965年 | 1篇 |
排序方式: 共有334条查询结果,搜索用时 15 毫秒
51.
Carl PC Chen Chih-Chin Hsu Wen-Lin Yeh Hsiu-Chu Lin Sen-Yung Hsieh Shih-Cherng Lin Tai-Tzung Chen Max JL Chen Simon FT Tang 《Proteome science》2011,9(1):1-10
Background
Prenatal screening for Down Syndrome (DS) would benefit from an increased number of biomarkers to improve sensitivity and specificity. Improving sensitivity and specificity would decrease the need for potentially risky invasive diagnostic procedures.Results
We have performed an in depth two-dimensional difference gel electrophoresis (2D DIGE) study to identify potential biomarkers. We have used maternal plasma samples obtained from first and second trimesters from mothers carrying DS affected fetuses compared with mothers carrying normal fetuses. Plasma samples were albumin/IgG depleted and expanded pH ranges of pH 4.5 - 5.5, pH 5.3 - 6.5 and pH 6 - 9 were used for two-dimensional gel electrophoresis (2DE). We found no differentially expressed proteins in the first trimester between the two groups. Significant up-regulation of ceruloplasmin, inter-alpha-trypsin inhibitor heavy chain H4, complement proteins C1s subcomponent, C4-A, C5, and C9 and kininogen 1 were detected in the second trimester in maternal plasma samples where a DS affected fetus was being carried. However, ceruloplasmin could not be confirmed as being consistently up-regulated in DS affected pregnancies by Western blotting.Conclusions
Despite the in depth 2DE approach used in this study the results underline the deficiencies of gel-based proteomics for detection of plasma biomarkers. Gel-free approaches may be more productive to increase the number of plasma biomarkers for DS for non-invasive prenatal screening and diagnosis. 相似文献52.
AB Kane RP Stanton EG Raymond ME Dobson ME Knafelc JL Farber 《The Journal of cell biology》1980,87(3):643-651
The relationship between intracellular lysosomal rupture and cell death caused by silica was studied in P388d(1) macrophages. After 3 h of exposure to 150 μg silica in medium containing 1.8 mM Ca(2+), 60 percent of the cells were unable to exclude trypan blue. In the absence of extracellular Ca(2+), however, all of the cells remained viable. Phagocytosis of silica particles occurred to the same extent in the presence or absence of Ca(2+). The percentage of P388D(1) cells killed by silica depended on the dose and the concentration of Ca(2+) in the medium. Intracellular lyosomal rupture after exposure to silica was measured by acridine orange fluorescence or histochemical assay of horseradish peroxidase. With either assay, 60 percent of the cells exposed to 150 μg silica for 3 h in the presence of Ca(2+) showed intracellular lysosomal rupture, was not associated with measureable degradation of total DNA, RNA, protein, or phospholipids or accelerated turnover of exogenous horseradish peroxidase. Pretreatment with promethazine (20 μg/ml) protected 80 percent of P388D(1) macrophages against silica toxicity although lysosomal rupture occurred in 60-70 percent of the cells. Intracellular lysosomal rupture was prevented in 80 percent of the cells by pretreatment with indomethacin (5 x 10(-5)M), yet 40-50 percent of the cells died after 3 h of exposure to 150 μg silica in 1.8 mM extracellular Ca(2+). The calcium ionophore A23187 also caused intracellular lysosomal rupture in 90-98 percent of the cells treated for 1 h in either the presence or absence of extracellular Ca(2+). With the addition of 1.8 mM Ca(2+), 80 percent of the cells was killed after 3 h, whereas all of the cells remained viable in the absence of Ca(2+). These experiments suggest that intracellular lysosomal rupture is not causally related to the cell death cause by silica or . Cell death is dependent on extracellular Ca(2+) and may be mediated by an influx of these ions across the plasma membrane permeability barrier damaged directly by exposure to these toxins. A23187相似文献
53.
The possibility of enhancing the ex situ bioremediation of a chronically polychlorinated biphenyl (PCB)-contaminated soil
by using Triton X-100 or Quillaya Saponin, a synthetic and a biogenic surfactant, respectively, was studied. The soil, which
contained about 350 mg/kg of PCBs and indigenous aerobic bacteria capable of growing on biphenyl or on monochlorobenzoic acids,
was amended with inorganic nutrients and biphenyl, saturated with water and treated in aerobic batch slurry- and fixed-phase
reactors. Triton X-100 and Quillaya Saponin were added to the reactors at a final concentration of 10 g/l at the 42nd day
of treatment, and at the 43rd and 100th day, respectively. Triton X-100 was not metabolised by the soil microflora and it
exerted inhibitory effects on the indigenous bacteria. Quillaya Saponin, on the contrary, was readily metabolised by the soil
microflora. Under slurry-phase conditions, Triton X-100 negatively influenced the soil bioremediation process by affecting
the availability of the chlorobenzoic acid degrading indigenous bacteria, whereas Quillaya Saponin slightly enhanced the biological
degradation and dechlorination of the soil PCBs. In the fixed-phase reactors, where both the surfactant availability and the
mixing of the soil were lower, Triton X-100 did not exert inhibitory effects on the soil biomass and enhanced significantly
the soil PCB depletion, whereas Quillaya Saponin did not influence the bioremediation process.
Received: 28 April 1998 / Received last revision: 15 July 1998 / Accepted: 29 July 1998 相似文献
54.
Koffler Christoph Amor Ben Carbajales-Dale Michael Cascio Joseph Conroy Alison Fava James A. Gaudreault Caroline Gloria Thomas Hensler Connie Horvath Arpad Humbert Sebastien Manzardo Alessandro Margni Manuele Osset Philippe Sinistore Julie Vigon Bruce Wallace Michele L Wang Michael Prox Martina 《The International Journal of Life Cycle Assessment》2020,25(3):478-482
The International Journal of Life Cycle Assessment - 相似文献
55.
56.
Plasminogen activator and collagenase production by cultured capillary endothelial cells 总被引:16,自引:17,他引:16 下载免费PDF全文
Cultured bovine capillary endothelial (BCE) cells produce low levels of collagenolytic activity and significant amounts of the serine protease plasminogen activator (PA). When grown in the presence of nanomolar quantities of the tumor promoter 12-O-tetradecanoyl phorbol-13-acetate (TPA), BCE cells produced 5-15 times more collagenolytic activity and 2-10 times more PA than untreated cells. The enhanced production of these enzymes was dependent on the dose of TPA used, with maximal response at 10(-7) to 10(-8) M. Phorbol didecanoate (PDD), an analog of TPA which is an active tumor promoter, also increased protease production. 4-O-methyl-TPA and 4α-PDD, two analogs of TPA which are inactive as tumor promoters, had no effect on protease production. Increased PA and collagenase activities were detected within 7.5 and 19 h, respectively, after the addition of TPA. The TPA-stimulated BCE cells synthesized a urokinase-type PA and a typical vertebrate collagenase. BCE cells were compared with bovine aortic endothelial (BAE) cells and bovine embryonic skin (BES) fibroblasts with respect to their production of protease in response to TPA. Under normal growth conditions, low levels of collagenolyic activity were detected in the culture fluids from BCE, BAE, and BES cells. BCE cells produced 5-13 times the basal levels of collagenolytic activity in response to TPA, whereas BAE cells and BES fibroblasts showed a minimal response to TPA. Both BCE and BAE cells exhibited relatively high basal levels of PA, the production of which was stimulated approximately threefold by the addition of TPA. The observation that BCE cells and not BAE cells produced high levels of both PA and collagenase activities in response to TPA demonstrates a significant difference between these two types of endothelial cells and suggests that the enhanced detectable activities are a property unique to bovine capillary and microvessel and endothelial cells. 相似文献
57.
Two distinct conformational states define the interaction of human RAD51‐ATP with single‐stranded DNA 下载免费PDF全文
Andrea Candelli Edwige B Garcin Mauro Modesti Luca Pellegrini Gijs JL Wuite Erwin JG Peterman 《The EMBO journal》2018,37(7)
An essential mechanism for repairing DNA double‐strand breaks is homologous recombination (HR). One of its core catalysts is human RAD51 (hRAD51), which assembles as a helical nucleoprotein filament on single‐stranded DNA, promoting DNA‐strand exchange. Here, we study the interaction of hRAD51 with single‐stranded DNA using a single‐molecule approach. We show that ATP‐bound hRAD51 filaments can exist in two different states with different contour lengths and with a free‐energy difference of ~4 kBT per hRAD51 monomer. Upon ATP hydrolysis, the filaments convert into a disassembly‐competent ADP‐bound configuration. In agreement with the single‐molecule analysis, we demonstrate the presence of two distinct protomer interfaces in the crystal structure of a hRAD51‐ATP filament, providing a structural basis for the two conformational states of the filament. Together, our findings provide evidence that hRAD51‐ATP filaments can exist in two interconvertible conformational states, which might be functionally relevant for DNA homology recognition and strand exchange. 相似文献
58.
Summary A crude extract of Alcaligenes sp. CPE3 strain grown on 3,4-dichlorobenzoic acid metabolised 3- and 4-chlorobenzoic acid by reactions requiring O2 and NADH, and 3,4-dichlorobenzoic acid by a reaction requiring O2, NADH, FAD and FMN. The specific activity of the extract vs. 3-chlorobenzoic acid was described by the Michaelis-Menten kinetics, that vs. 4-chlorobenzoic acid was described by a substrate inhibitory kinetics and that vs. 3,4-dichlorobenzoic acid exhibited a two-peaked profile. 相似文献
59.
C Zinner M Krueger JL Reed M Kohl-Bareis H-C Holmberg B Sperlich 《Biology of sport / Institute of Sport》2016,33(1):71-76
In this study, we tested the hypothesis that breathing hyperoxic air (FinO2 = 0.40) while exercising in a hot environment exerts negative effects on the total tissue level of haemoglobin concentration (tHb); core (Tcore) and skin (Tskin) temperatures; muscle activity; heart rate; blood concentration of lactate; pH; partial pressure of oxygen (PaO2) and carbon dioxide; arterial oxygen saturation (SaO2); and perceptual responses. Ten well-trained male athletes cycled at submaximal intensity at 21°C or 33°C in randomized order: first for 20 min while breathing normal air (FinO2 = 0.21) and then 10 min with FinO2 = 0.40 (HOX). At both temperatures, SaO2 and PaO2, but not tHb, were increased by HOX. Tskin and perception of exertion and thermal discomfort were higher at 33°C than 21°C (p < 0.01), but independent of FinO2. Tcore and muscle activity were the same under all conditions (p > 0.07). Blood lactate and heart rate were higher at 33°C than 21°C. In conclusion, during 30 min of submaximal cycling at 21°C or 33°C, Tcore, Tskin and Tbody, tHb, muscle activity and ratings of perceived exertion and thermal discomfort were the same under normoxic and hyperoxic conditions. Accordingly, breathing hyperoxic air (FinO2 = 0.40) did not affect thermoregulation under these conditions. 相似文献
60.
Histological distribution of the 35-KD protein substrate of the epidermal growth factor receptor/kinase in thymus 总被引:1,自引:0,他引:1
Rat thymus has been identified as a tissue comparatively enriched in a 35-KD substrate of the epidermal growth factor receptor/kinase (lipocortin-1) (J Biol Chem 261:13784, 1986). A polyclonal antiserum prepared against the 35-KD protein was used to determine histological distribution of the protein in thymus. Frozen sections of rat thymus were examined after indirect labeling of the 35-KD protein with a rhodamine conjugate of secondary antibody. The antigen was localized primarily in the reticular network of the thymic epithelium, with no detectable labeling of resident thymocytes. Immunoblotting (Western blots) of cytosol extracts also demonstrated that thymocytes did not contain detectable amounts of the antigen. Cultured thymic epithelial cells (TEC), however, contained an abundance of two immunologically related protein bands with molecular weights similar but not identical to the antigen from the parental cell line (human A-431 carcinoma). Paraffin sections of rat and human thymus were subjected to an immunoperoxidase staining procedure, and it was observed that Hassall's corpuscles (keratinized epithelial cells) and other cortical and medullary TECs were intensely stained. The demonstration that the antigen is primarily associated with TEC in thymus, in conjunction with its distribution in other tissues, will aid in deducing its physiological role. 相似文献