全文获取类型
收费全文 | 537篇 |
免费 | 27篇 |
出版年
2023年 | 4篇 |
2022年 | 3篇 |
2021年 | 7篇 |
2020年 | 7篇 |
2019年 | 4篇 |
2018年 | 6篇 |
2017年 | 3篇 |
2016年 | 14篇 |
2015年 | 23篇 |
2014年 | 24篇 |
2013年 | 34篇 |
2012年 | 55篇 |
2011年 | 37篇 |
2010年 | 34篇 |
2009年 | 23篇 |
2008年 | 32篇 |
2007年 | 33篇 |
2006年 | 34篇 |
2005年 | 25篇 |
2004年 | 15篇 |
2003年 | 14篇 |
2002年 | 21篇 |
2001年 | 4篇 |
1999年 | 5篇 |
1998年 | 10篇 |
1997年 | 6篇 |
1995年 | 6篇 |
1994年 | 5篇 |
1993年 | 6篇 |
1992年 | 4篇 |
1991年 | 3篇 |
1990年 | 3篇 |
1989年 | 4篇 |
1988年 | 6篇 |
1987年 | 6篇 |
1985年 | 3篇 |
1984年 | 2篇 |
1980年 | 3篇 |
1978年 | 2篇 |
1977年 | 3篇 |
1975年 | 4篇 |
1974年 | 3篇 |
1972年 | 2篇 |
1964年 | 2篇 |
1961年 | 4篇 |
1955年 | 1篇 |
1954年 | 1篇 |
1944年 | 1篇 |
1943年 | 1篇 |
1932年 | 1篇 |
排序方式: 共有564条查询结果,搜索用时 31 毫秒
21.
Howell GJ Herbert SP Smith JM Mittar S Ewan LC Mohammed M Hunter AR Simpson N Turner AJ Zachary I Walker JH Ponnambalam S 《Molecular membrane biology》2004,21(6):413-421
Secretory granules called Weibel-Palade bodies (WPBs) containing Von Willebrand factor (VWF) are characteristic of the mammalian endothelium. We hypothesized that vascular-specific antigens such as VWF are linked to endothelial identity and proliferation in vitro. To test this idea, the cellular accumulation of VWF in WPBs was monitored as a function of cell proliferation, confluence and passage number in human umbilical vein endothelial cells (HUVECs). We found that as passage number increased the percentage of cells containing VWF in WPBs was reduced significantly, whilst the protein was still detected within the secretory pathway at all times. However, the endothelial-specific marker protein, PECAM-1, is present on all cells even when WPBs are absent, indicating partial maintenance of endothelial identity. Biochemical studies show that a significant pool of immature pro-VWF can be detected in sub-confluent HUVECs; however, a larger pool of mature, processed VWF is detected in confluent cells. Newly synthesized VWF must thus be differentially sorted and packaged along the secretory pathway in semi-confluent versus confluent endothelial cells. Our studies thus show that WPB formation is linked to the formation of a confluent endothelial monolayer. 相似文献
22.
Computational methods for generating models of denatured and partially folded proteins 总被引:2,自引:0,他引:2
Smith LJ 《Methods (San Diego, Calif.)》2004,34(1):144-150
Partially folded and denatured proteins can give important insights into protein folding, misfolding, and aggregation. Such non-native states of proteins are however very difficult to characterise in detail as they are dynamic, heterogeneous systems comprising of ensembles of interconverting conformers. This article describes methods that produce models for non-native proteins in atomic detail. A variety of molecular dynamics based protocols are discussed together with some recent procedures that include restraints from experimental data. These models provide an important framework for interpreting experimental data from studies of non-native states using nuclear magnetic resonance spectroscopy, fluorescence, circular dichroism, and small angle scattering techniques. 相似文献
23.
In situ (13)C pulse labelling was used to measure the temporal and spatial carbon flow through an upland grassland. The label was delivered as (13)C-CO(2) to vegetation in three replicate plots in each of two treatments: control and lime addition. Harvests occurred over a two month period and samples were taken along transects away from the label delivery area. The (13)C concentration of shoot, root, bulk soil, and soil-respired CO(2) was measured. There was no difference in the biomass and (13)C concentration of shoot and root material for the control and lime treatments meaning that the amount of (13)C-CO(2) assimilated by the vegetation and translocated below ground was the same in both treatments. The (13)C concentration of the bulk soil was lower in the lime treatment than in the control and, conversely, the (13)C concentration of the soil-respired CO(2) was higher in the lime. Unlike the difference in bulk soil (13)C concentration between treatments, the difference in the (13)C concentration of the soil-respired CO(2) was obvious only at the delivery site and primarily within 1 d after labelling. An observed increase in the abundance of mycorrhizal fungi in the lime treatment was a possible cause for this faster carbon throughput. The potential key role of mycorrhizas in the soil carbon cycle is discussed. The importance of a better understanding of soil processes, especially biological ones, in relation to the global carbon cycle and environmental change is highlighted. 相似文献
24.
Back signaling by the Nrg-1 intracellular domain 总被引:4,自引:0,他引:4
Transmembrane isoforms of neuregulin-1 (Nrg-1), ligands for erbB receptors, include an extracellular domain with an EGF-like sequence and a highly conserved intracellular domain (ICD) of unknown function. In this paper, we demonstrate that transmembrane isoforms of Nrg-1 are bidirectional signaling molecules in neurons. The stimuli for Nrg-1 back signaling include binding of erbB receptor dimers to the extracellular domain of Nrg-1 and neuronal depolarization. These stimuli elicit proteolytic release and translocation of the ICD of Nrg-1 to the nucleus. Once in the nucleus, the Nrg-1 ICD represses expression of several regulators of apoptosis, resulting in decreased neuronal cell death in vitro. Thus, regulated proteolytic processing of Nrg-1 results in retrograde signaling that appears to mediate contact and activity-dependent survival of Nrg-1-expressing neurons. 相似文献
25.
Protein kinase B/Akt prevents fatty acid-induced apoptosis in pancreatic beta-cells (INS-1) 总被引:30,自引:0,他引:30
Wrede CE Dickson LM Lingohr MK Briaud I Rhodes CJ 《The Journal of biological chemistry》2002,277(51):49676-49684
26.
Naturally occurring mutations in the largest extracellular loops of ABCA1 can disrupt its direct interaction with apolipoprotein A-I 总被引:8,自引:0,他引:8
Fitzgerald ML Morris AL Rhee JS Andersson LP Mendez AJ Freeman MW 《The Journal of biological chemistry》2002,277(36):33178-33187
The ABCA1 transporter contains two large domains into which many of the genetic mutations in individuals with Tangier disease fall. To investigate the structural requirements for the cellular cholesterol efflux mediated by ABCA1, we have determined the topology of these two domains and generated transporters harboring five naturally occurring missense mutations in them. These mutants, unlike wild type ABCA1, produced little or no apoA-I-stimulated cholesterol efflux when transfected into 293 cells, establishing their causality in Tangier disease. Because all five mutant proteins were well expressed and detectable on the plasma membrane, their interaction with the ABCA1 ligand, apolipoprotein (apo) A-I, was measured using bifunctional cross-linking agents. Four of five mutants had a marked decline in cross-linking to apoA-I, whereas one (W590S) retained full cross-linking activity. Cross-linking of apoA-I was temperature-dependent, rapid in onset, and detectable with both lipid- and water-soluble cross-linking agents. These results suggest that apoA-I-stimulated cholesterol efflux cannot occur without a direct interaction between the apoprotein and critical residues in two extracellular loops of ABCA1. The behavior of the W590S mutant indicates that although binding of apoA-I by ABCA1 may be necessary, it is not sufficient for stimulation of cholesterol efflux. 相似文献
27.
Stearne LE Schiffelers RM Smouter E Bakker-Woudenberg IA Gyssens IC 《Biochimica et biophysica acta》2002,1561(1):91-97
The biodistribution of long-circulating PEG-liposomes in a subcutaneous mouse model of established mixed infection abscesses was investigated to assess their possible role as drug carriers in the treatment of small, undrainable intra-abdominal abscesses. There was a 10-30-fold greater localisation of (67)Ga-labelled PEG-liposomes in abscesses compared to uninfected normal skin samples. Over 3% of the injected dose (ID) of liposomes was present in the abscesses 24 h after liposome administration in contrast to 0.1% in normal skin sections. The percentage ID present in the liver, spleen and kidneys was 17%, 4% and 2% per organ respectively. Five days after liposome injection, 2% ID could still be recovered from the abscesses. Using colloidal gold-labelled PEG-liposomes, it was shown that there was a 4-fold greater density of liposome clusters in the subcutaneous tissue surrounding the capsule than in the core of the abscesses. The clusters within the abscesses were distributed evenly. We conclude that PEG-liposomes localise to a significant degree at the infection focus in our mouse model and may provide a new approach to the antimicrobial treatment of intra-abdominal abscesses. 相似文献
28.
Extended Survival and Persistence of Campylobacter spp. in Water and Aquatic Biofilms and Their Detection by Immunofluorescent-Antibody and -rRNA Staining 总被引:4,自引:0,他引:4 下载免费PDF全文
Clive M. Buswell Yvonne M. Herlihy Lorna M. Lawrence James T. M. McGuiggan Philip D. Marsh C. William Keevil Steve A. Leach 《Applied microbiology》1998,64(2):733-741
In water microcosm experiments, the survival times of Campylobacter isolates differed by up to twofold, as determined by culturing; this difference increased to fourfold when particular combinations of temperature and oxygenation were used. The mean survival times were much longer at 4 and 10°C (202 and 176 h, respectively) than at 22 and 37°C (43 and 22 h, respectively). The influence of anaerobiosis on survival time was less dramatic and differed considerably between isolates. In a two-stage water distribution model preparation containing a biofilm consisting of standardized autochthonous water microflora, Campylobacter isolates continued to differ in survival time. However, the survival times of cultures were considerably longer in the presence of the autochthonous water microflora (strains CH1 and 9752 survived 700 and 360 h, respectively, at 4°C) than in the sterile microcosms (strains CH1 and 9752 survived 230 and 157 h, respectively). Although increased temperature and oxygenation were generally detrimental to culturability, the interaction of these two factors influenced the two strains examined differently. When the organisms were grown aerobically at 30°C, the survival of the two strains was reversed; aerobiosis decreased the survival time of strain CH1 by 30%, but unexpectedly improved the persistence time of strain 9752 by more than threefold. Persistence times within biofilms were much longer when they were determined by detection methods not involving culturing. Immunofluorescent-antibody staining demonstrated that the pathogen persisted up to the termination of the experiments after 28 and 42 days of incubation at 30 and 4°C, respectively. The specificity of detection within intact biofilms was reduced because of high background fluorescence. However, preliminary studies with a Campylobacter-specific rRNA probe revealed the same extended persistence of the pathogen within the biofilms. 相似文献
29.
Abstract. 1. This study evaluated the effect of dispersal on the density and feeding impact of a phytophagous insect in relation to the spatial distribution of its host plants.
2. The interaction between density, dispersal, and feeding impact of western flower thrips on flowering chrysanthemum was quantified at three spatial scales, with infested and uninfested plants either isolated in 0.25 m2 individual cages, or enclosed together in 2.25 m2 communal cages or 75 m2 greenhouses.
3. In individual cages, the rate of dispersal from chrysanthemum plants to blue sticky traps increased with the density of thrips for females but not males. Uninfested plants consistently had fewer thrips when they were individually caged rather than enclosed with plants infested with adults, indicating that dispersal mediates inter-plant distribution of thrips.
4. The feeding impact of thrips on inflorescences was evaluated using the absorbance of ethanol extracts at wavelengths characteristic of yellow carotenoid pigments associated with chrysanthemum inflorescences (415, 445, and 472 nm). Increasing absorbance of extracts with increasing density of thrips per inflorescence suggests that feeding by thrips results in ruptured cells leaching carotenoid pigments.
5. In communal cages, the distribution of thrips was uniform for infested and uninfested plants, whereas the density and feeding impact of thrips in greenhouses were higher for infested than uninfested plants. These results suggest that short-range dispersal by adults homogenises the density and feeding impact of thrips among host plants only on a small spatial scale. 相似文献
2. The interaction between density, dispersal, and feeding impact of western flower thrips on flowering chrysanthemum was quantified at three spatial scales, with infested and uninfested plants either isolated in 0.25 m
3. In individual cages, the rate of dispersal from chrysanthemum plants to blue sticky traps increased with the density of thrips for females but not males. Uninfested plants consistently had fewer thrips when they were individually caged rather than enclosed with plants infested with adults, indicating that dispersal mediates inter-plant distribution of thrips.
4. The feeding impact of thrips on inflorescences was evaluated using the absorbance of ethanol extracts at wavelengths characteristic of yellow carotenoid pigments associated with chrysanthemum inflorescences (415, 445, and 472 nm). Increasing absorbance of extracts with increasing density of thrips per inflorescence suggests that feeding by thrips results in ruptured cells leaching carotenoid pigments.
5. In communal cages, the distribution of thrips was uniform for infested and uninfested plants, whereas the density and feeding impact of thrips in greenhouses were higher for infested than uninfested plants. These results suggest that short-range dispersal by adults homogenises the density and feeding impact of thrips among host plants only on a small spatial scale. 相似文献
30.
Gloria Omosa-Manyonyi Juliet Mpendo Eugene Ruzagira William Kilembe Elwyn Chomba Fran?ois Roman Patricia Bourguignon Marguerite Koutsoukos Alix Collard Gerald Voss Dagna Laufer Gwynn Stevens Peter Hayes Lorna Clark Emmanuel Cormier Len Dally Burc Barin Jim Ackland Kristen Syvertsen Devika Zachariah Kamaal Anas Eddy Sayeed Angela Lombardo Jill Gilmour Josephine Cox Patricia Fast Frances Priddy 《PloS one》2015,10(5)