全文获取类型
收费全文 | 115篇 |
免费 | 8篇 |
出版年
2022年 | 1篇 |
2021年 | 2篇 |
2020年 | 2篇 |
2019年 | 3篇 |
2018年 | 2篇 |
2017年 | 5篇 |
2016年 | 5篇 |
2015年 | 4篇 |
2014年 | 5篇 |
2013年 | 10篇 |
2012年 | 4篇 |
2011年 | 4篇 |
2010年 | 7篇 |
2009年 | 7篇 |
2008年 | 6篇 |
2007年 | 3篇 |
2006年 | 4篇 |
2005年 | 2篇 |
2004年 | 5篇 |
2003年 | 3篇 |
2002年 | 1篇 |
2001年 | 2篇 |
2000年 | 4篇 |
1999年 | 1篇 |
1998年 | 11篇 |
1997年 | 2篇 |
1996年 | 1篇 |
1991年 | 2篇 |
1990年 | 1篇 |
1989年 | 1篇 |
1987年 | 1篇 |
1984年 | 1篇 |
1983年 | 1篇 |
1982年 | 2篇 |
1981年 | 2篇 |
1979年 | 1篇 |
1973年 | 1篇 |
1971年 | 1篇 |
1966年 | 1篇 |
1961年 | 1篇 |
1959年 | 1篇 |
排序方式: 共有123条查询结果,搜索用时 15 毫秒
1.
Collagen metabolism in mouse lung after X irradiation 总被引:1,自引:0,他引:1
Collagen and total protein synthesis rates have been determined in the lungs of CBA mice irradiated with single doses of X rays between 8 and 16 Gy. Mice were injected with [3H]proline accompanied by a large dose of unlabeled proline, and synthesis rates were measured at 2-month intervals from 8 to 31 weeks after irradiation. At 2 months after radiation treatment, collagen and total protein synthesis rates were significantly depressed but they had recovered by 4 months. By 6 months collagen synthesis rates had increased above control in a dose-dependent manner, so that in the 14-Gy dose group the fractional synthesis rate for collagen was 4.6 times higher than in control mice as measured by incorporation of [3H]proline. However, a significant net accumulation of collagen was seen only in the lungs of the highest dose group at 31 weeks, as indicated by total hydroxyproline measurements. There was a slight increase in the ratio of types I and III collagen. Late radiation damage in the CBA mouse lung is characterized by increased collagen metabolism, which may or may not lead to a net accumulation of collagen. 相似文献
2.
CJ von Ruhland 《Biotechnic & histochemistry》2013,88(7):478-484
Amplification of immunohistochemical markers received considerable attention during the 1980s and 1990s. The amplification approach was largely abandoned following the development of antigen retrieval and reporter amplification techniques, because the latter were incorporated more easily into high throughput automated procedures in industrial and diagnostic laboratories. There remain, however, a number of instances where marker amplification still has much to offer. Consequently, we examined experimentally the utility of an optimized marker amplification technique in diagnostically relevant tissue where either the original signal strength was low or positive sites were visible, but sparsely distributed. Marker amplification in the former case not only improved the visibility of existing positive sites, but also revealed additional sites that previously were undetectable. In the latter case, positive sites were rendered more intense and therefore more easily seen during low magnification examination of large areas of tissue. 相似文献
3.
The experiment was organized in a 3×2 factorial arrangement with three dietary fat blends and a basal (20 mg kg?1 diet) or supplemented (220 mg kg?1) level of α-tocopheryl acetate. Dietary vitamin E and monounsaturated to polyunsaturated fatty acid ratio (dietary MUFA/PUFA) affected muscle α-tocopherol concentration (α-tocopherol [log μg g?1]=0.18 (±0.105)+0.0034 (±0.0003)·dietary α-tocopherol [mg kg?1 diet] (P<0.0001)+0.39 (±0.122)·dietary MUFA/PUFA (P<0.0036)). An interaction between dietary α-tocopherol and dietary MUFA/PUFA exists for microsome α-tocopherol concentration (α-tocopherol [log μg g?1]=1.14 (±0.169) (P<0.0001)+0.0056 (±0.00099)·dietary α-tocopherol [mg kg?1 diet] (P<0.0001)+0.54 (±0.206)·dietary MUFA/PUFA (P<0.0131)?0.0033 (±0.0011)·dietary α-tocopherol [mg kg?1)]×dietary MUFA/PUFA (P<0.0067)), and hexanal concentration in meat (hexanal [ng·g?1]=14807.9 (±1489.8)?28.8 (±10.6) dietary α-tocopherol [mg·kg?1] (P<0.01)?8436.6 (±1701.6)·dietary MUFA/PUFA (P<0.001)+24.0 (±11.22)·dietary α-tocopherol·dietary MUFA/PUFA (P<0.0416)). It is concluded that partial substitution of dietary PUFA with MUFA lead to an increase in the concentration of α-tocopherol in muscle and microsome extracts. An interaction between dietary α-tocopherol and fatty acids exists, in which at low level of dietary vitamin E inclusion, a low MUFA/PUFA ratio leads to a reduction in the concentration of α-tocopherol in microsome extracts and a concentration of hexanal in meat above the expected values. 相似文献
4.
CJ Cooksey 《Biotechnic & histochemistry》2016,91(1):71-76
Rhodamines were first produced in the late 19th century, when they constituted a new class of synthetic dyes. These compounds since have been used to color many things including cosmetics, inks, textiles, and in some countries, food products. Certain rhodamine dyes also have been used to stain biological specimens and currently are widely used as fluorescent probes for mitochondria in living cells. The early history and current biological applications are sketched briefly and an account of the ambiguities, complications and confusions concerning dye identification and nomenclature are discussed. 相似文献
5.
CJ Cooksey 《Biotechnic & histochemistry》2016,91(6):438-444
Malachite green was discovered independently by two researchers in Germany in the 19th century and found immediate employment as a dye and a pigment. Subsequently, other uses, such as staining biological specimens, emerged. A much later application was the control of fungal and protozoan infections in fish, for which the dye remains popular, although illegal in many countries owing to a variety of toxicity problems. In solution, malachite green can exist as five different species depending on the pH. The location of the positive charge of the colored cation on a carbon atom or a nitrogen atom is still debated. The original names of this dye, and their origins, are briefly surveyed. 相似文献
6.
David D. Feehan Khusraw Jamil Maria J. Polyak Henry Ogbomo Mark Hasell Shu Shun LI Richard F. Xiang Michael Parkins Joseph A. Trapani Joe J. Harrison Christopher H. Mody 《PLoS pathogens》2022,18(2)
Pseudomonas aeruginosa is an opportunistic pathogen that often infects individuals with the genetic disease cystic fibrosis, and contributes to airway blockage and loss of lung function. Natural killer (NK) cells are cytotoxic, granular lymphocytes that are part of the innate immune system. NK cell secretory granules contain the cytolytic proteins granulysin, perforin and granzymes. In addition to their cytotoxic effects on cancer and virally infected cells, NK cells have been shown to play a role in an innate defense against microbes, including bacteria. However, it is not known if NK cells kill extracellular P. aeruginosa or how bacterial killing might occur at the molecular level. Here we show that NK cells directly kill extracellular P. aeruginosa using NK effector molecules. Live cell imaging of a co-culture of YT cells, a human NK cell line, and GFP-expressing P. aeruginosa in the presence of the viability dye propidium iodide demonstrated that YT cell killing of P. aeruginosa is contact-dependent. CRISPR knockout of granulysin or perforin in YT cells had no significant effect on YT cell killing of P. aeruginosa. Pre-treatment of YT and NK cells with the serine protease inhibitor 3,4-dichloroisocoumarin (DCI) to inhibit all granzymes, resulted in an inhibition of killing. Although singular CRISPR knockout of granzyme B or H had no effect, knockout of both in YT cells completely abrogated killing of P. aeruginosa in comparison to wild type YT cell controls. Nitrocefin assays suggest that the bacterial membrane is damaged. Inhibition of killing by antioxidants suggest that ROS are required for the bactericidal mode-of-action. Taken together, these results identify that NK cells kill P. aeruginosa through a membrane damaging, contact-dependent process that requires granzyme induced ROS production, and moreover, that granzyme B and H are redundant in this killing process. 相似文献
7.
Phosphoinositides,ezrin/moesin,and rac1 regulate fusion of rhodopsin transport carriers in retinal photoreceptors
下载免费PDF全文
![点击此处可从《Molecular biology of the cell》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Deretic D Traverso V Parkins N Jackson F Rodriguez de Turco EB Ransom N 《Molecular biology of the cell》2004,15(1):359-370
The post-Golgi trafficking of rhodopsin in photoreceptor cells is mediated by rhodopsin-bearing transport carriers (RTCs) and regulated by the small GTPase rab8. In this work, we took a combined pharmacological-proteomic approach to uncover new regulators of RTC trafficking toward the specialized light-sensitive organelle, the rod outer segment (ROS). We perturbed phospholipid synthesis by activating phospholipase D with sphingosine 1-phosphate (S1P) or inhibiting phosphatidic acid phosphohydrolase by propranolol (Ppl). S1P stimulated the overall rate of membrane trafficking toward the ROS. Ppl stimulated budding of RTCs, but blocked membrane delivery to the ROS. Ppl caused accumulation of RTCs in the vicinity of the fusion sites, suggesting a defect in tethering, similar to the previously described phenotype of the rab8T22N mutant. Proteomic analysis of RTCs accumulated upon Ppl treatment showed a significant decrease in phosphatidylinositol-4,5-bisphosphate-binding proteins ezrin and/or moesin. Ppl induced redistribution of moesin, actin and the small GTPase rac1 from RTCs into the cytosol. By confocal microscopy, ezrin/moesin and rac1 colocalized with rab8 on RTCs at the sites of their fusion with the plasma membrane; however, this distribution was lost upon Ppl treatment. Our data suggest that in photoreceptors phosphatidylinositol-4,5-bisphosphate, moesin, actin, and rac1 act in concert with rab8 to regulate tethering and fusion of RTCs. Consequentially, they are necessary for rhodopsin-laden membrane delivery to the ROS, thus controlling the critical steps in the biogenesis of the light-detecting organelle. 相似文献
8.
K J Parkins C F Poets L M O’Brien V A Stebbens D P Southall 《BMJ (Clinical research ed.)》1998,316(7135):887-894
Objective: To assess the response of healthy infants to airway hypoxia (15% oxygen in nitrogen). Design: Interventional study. Settings: Infants’ homes and paediatric ward. Subjects: 34 healthy infants (20 boys) born at term; mean age at study 3.1 months. 13 of the infants had siblings whose deaths had been ascribed to the sudden infant death syndrome. Intervention: Respiratory variables were measured in room air (pre-challenge), while infants were exposed to 15% oxygen (challenge), and after infants were returned to room air (post-challenge). Main outcome measures: Baseline oxygen saturation as measured by pulse oximetry, frequency of isolated and periodic apnoea, and frequency of desaturation (oxygen saturation ⩽80% for ⩾4 s). Exposure to 15% oxygen was terminated if oxygen saturation fell to ⩽80% for ⩾1 min. Results: Mean duration of exposure to 15% oxygen was 6.3 (SD 2.9) hours. Baseline oxygen saturation fell from a median of 97.6% (range 94.0% to 100%) in room air to 92.8% (84.7% to 100%) in 15% oxygen. There was no correlation between baseline oxygen saturation in room air and the extent of the fall in baseline oxygen saturation on exposure to 15% oxygen. During exposure to 15% oxygen there was a reduction in the proportion of time spent in regular breathing pattern and a 3.5-fold increase in the proportion of time spent in periodic apnoea (P<0.001). There was an increase in the frequency of desaturation from 0 episodes per hour (range 0 to 0.2) to 0.4 episodes per hour (0 to 35) (P<0.001). In 4 infants exposure to hypoxic conditions was ended early because of prolonged and severe falls in oxygen saturation. Conclusions: A proportion of infants had episodes of prolonged (⩽80% for ⩾1 min) or recurrent shorter (⩽80% for ⩾4 s) desaturation, or both, when exposed to airway hypoxia. The quality and quantity of this response was unpredictable. These findings may explain why some infants with airway hypoxia caused by respiratory infection develop more severe hypoxaemia than others. Exposure to airway hypoxia similar to that experienced during air travel or on holiday at high altitude may be harmful to some infants.
Key messages
- A reduction in inspired oxygen concentration to 15% can induce severe prolonged hypoxaemia in a small proportion of infants
- Prediction of which infants will become hypoxaemic does not appear possible from analysing oxygenation or the respiratory pattern of infants breathing room air at sea level
- The way in which an infant responds to airway hypoxia may contribute to understanding the relation between respiratory infections, hypoxaemic episodes, and the sudden infant death syndrome
- Airline travel and holidays at high altitude may result in hypoxaemia in a small proportion of infants
9.
Ben C Collins Ludovic CJ Gillet Lorenz C Blum Lin‐Yang Cheng Olga Vitek Jeppe Mouritsen Genevieve Lachance Tim D Spector Emmanouil T Dermitzakis Ruedi Aebersold 《Molecular systems biology》2015,11(2)
The degree and the origins of quantitative variability of most human plasma proteins are largely unknown. Because the twin study design provides a natural opportunity to estimate the relative contribution of heritability and environment to different traits in human population, we applied here the highly accurate and reproducible SWATH mass spectrometry technique to quantify 1,904 peptides defining 342 unique plasma proteins in 232 plasma samples collected longitudinally from pairs of monozygotic and dizygotic twins at intervals of 2–7 years, and proportioned the observed total quantitative variability to its root causes, genes, and environmental and longitudinal factors. The data indicate that different proteins show vastly different patterns of abundance variability among humans and that genetic control and longitudinal variation affect protein levels and biological processes to different degrees. The data further strongly suggest that the plasma concentrations of clinical biomarkers need to be calibrated against genetic and temporal factors. Moreover, we identified 13 cis‐SNPs significantly influencing the level of specific plasma proteins. These results therefore have immediate implications for the effective design of blood‐based biomarker studies. 相似文献
10.