全文获取类型
收费全文 | 347篇 |
免费 | 17篇 |
出版年
2022年 | 5篇 |
2021年 | 3篇 |
2020年 | 5篇 |
2019年 | 5篇 |
2018年 | 7篇 |
2017年 | 5篇 |
2016年 | 10篇 |
2015年 | 23篇 |
2014年 | 14篇 |
2013年 | 21篇 |
2012年 | 32篇 |
2011年 | 33篇 |
2010年 | 26篇 |
2009年 | 14篇 |
2008年 | 32篇 |
2007年 | 31篇 |
2006年 | 27篇 |
2005年 | 16篇 |
2004年 | 15篇 |
2003年 | 5篇 |
2002年 | 16篇 |
2001年 | 1篇 |
2000年 | 3篇 |
1999年 | 3篇 |
1998年 | 2篇 |
1993年 | 1篇 |
1992年 | 3篇 |
1991年 | 3篇 |
1989年 | 2篇 |
1981年 | 1篇 |
排序方式: 共有364条查询结果,搜索用时 31 毫秒
171.
Katri Raikkonen Eero Kajantie Anu-Katriina Pesonen Kati Heinonen Hanna Alastalo Jukka T. Leskinen Kai Nyman Markus Henriksson Jari Lahti Marius Lahti Riikka Pyh?l? Soile Tuovinen Clive Osmond David J. P. Barker Johan G. Eriksson 《PloS one》2013,8(1)
Objectives
To examine whether the adverse effects of slow prenatal and postnatal growth on cognitive function persist to old age and predict age related cognitive decline.Design and Setting
A longitudinal birth cohort study of men born in Helsinki, Finland 1934-44.Participants
Nine-hundred-thirty-one men of the Helsinki Birth Cohort Study, with detailed data on growth from birth to adulthood, aged 20.1 (SD = 1.4) at the first and 67.9 (SD = 2.5) years at the second cognitive testing.Main Outcome Measures
The Finnish Defense Forces Basic Intellectual Ability Test assessed twice over nearly five decades apart.Results
Lower weight, length and head circumference at birth were associated with lower cognitive ability at 67.9 years (1.04–1.55 points lower ability per each standard deviation [SD] unit decrease in body size, 95% Confidence Interval [95%CI]: 0.05 to 2.72) and with cognitive decline after 20.1 years (0.07–0.11 SD decline over time per each SD decrease in body size, 95%CI:0.00 to 0.19). Men who were born larger were more likely to perform better in the cognitive ability test over time (1.22–1.43 increase in odds to remain in the top relative to the lower two thirds in ability over time per each SD increase in body size, 95%CI:1.04 to 1.79) and were more resilient to cognitive decline after 20.1 years (0.69 to 0.76 decrease in odds to decline from than remain in the top third of ability over time per each SD increase in body size, 95%CI:0.49 to 0.99). Slower growth between birth and two years in weight, height and body mass index was associated with lower cognitive ability at 67.9 years, but not with cognitive decline.Conclusions
Poorer lifetime cognitive ability is predicted by slower growth before and after birth. In predicting resilience to age related cognitive decline, the period before birth seems to be more critical. 相似文献172.
173.
Hassinen A Pujol FM Kokkonen N Pieters C Kihlström M Korhonen K Kellokumpu S 《The Journal of biological chemistry》2011,286(44):38329-38340
Glycosylation is one of the most common modifications of proteins and lipids and also a major source of biological diversity in eukaryotes. It is critical for many basic cellular functions and recognition events that range from protein folding to cell signaling, immunological defense, and the development of multicellular organisms. Glycosylation takes place mainly in the endoplasmic reticulum and Golgi apparatus and involves dozens of functionally distinct glycosidases and glycosyltransferases. How the functions of these enzymes, which act sequentially and often competitively, are coordinated to faithfully synthesize a vast array of different glycan structures is currently unclear. Here, we investigate the supramolecular organization of the Golgi N- and O-glycosylation pathways in live cells using a FRET flow cytometric quantification approach. We show that the enzymes form enzymatically active homo- and/or heteromeric complexes within each pathway. However, no complexes composed of enzymes that operate in different pathways, were detected, which suggests that the pathways are physically distinct. In addition, we show that complex formation is mediated almost exclusively by the catalytic domains of the interacting enzymes. Our data also suggest that the heteromeric complexes are functionally more important than enzyme homomers. Heteromeric complex formation was found to be dependent on Golgi acidity, markedly impaired in acidification-defective cancer cells, and required for the efficient synthesis of cell surface glycans. Collectively, the results emphasize that the Golgi glycosylation pathways are functionally organized into complexes that are important for glycan synthesis. 相似文献
174.
Hutchinson DK Flentge CA Donner PL Wagner R Maring CJ Kati WM Liu Y Masse SV Middleton T Mo H Montgomery D Jiang WW Koev G Beno DW Stewart KD Stoll VS Molla A Kempf DJ 《Bioorganic & medicinal chemistry letters》2011,21(6):1876-1879
A series of quinoline derivatives was synthesized as potential bioisosteric replacements for the benzothiadiazine moiety of earlier Hepatitis C NS5B polymerase inhibitors. Several of these compounds exhibited potent activity in enzymatic and replicon assays. 相似文献
175.
176.
177.
178.
Cellulase production using different streams of wheat grain- and wheat straw-based ethanol processes
Miklós Gyalai-Korpos Réka Mangel Pablo Alvira Dóra Dienes Mercedes Ballesteros Kati Réczey 《Journal of industrial microbiology & biotechnology》2011,38(7):791-802
Pretreatment is a necessary step in the biomass-to-ethanol conversion process. The side stream of the pretreatment step is
the liquid fraction, also referred to as the hydrolyzate, which arises after the separation of the pretreated solid and is
composed of valuable carbohydrates along with compounds that are potentially toxic to microbes (mainly furfural, acetic acid,
and formic acid). The aim of our study was to utilize the liquid fraction from steam-exploded wheat straw as a carbon source
for cellulase production by Trichoderma
reesei RUT C30. Results showed that without detoxification, the fungus failed to utilize any dilution of the hydrolyzate; however,
after a two-step detoxification process, it was able to grow on a fourfold dilution of the treated liquid fraction. Supplementation
of the fourfold-diluted, treated liquid fraction with washed pretreated wheat straw or ground wheat grain led to enhanced
cellulase (filter paper) activity. Produced enzymes were tested in hydrolysis of washed pretreated wheat straw. Supplementation
with ground wheat grain provided a more efficient enzyme mixture for the hydrolysis by means of the near-doubled β-glucosidase
activity obtained. 相似文献
179.
180.
Devraj Basu Kathleen T Montone Li-Ping Wang Phyllis A Gimotty Rachel Hammond J Alan Diehl Anil K Rustgi John T Lee Kati Rasanen Gregory S Weinstein Meenhard Herlyn 《Cell cycle (Georgetown, Tex.)》2011,10(12):2008-2016
Curative eradication of all cells within carcinomas is seldom achievable with chemotherapy alone. This limitation may be partially attributable to tumor cell subpopulations with intrinsic resistance to current drugs. Within squamous cell carcinoma (SCC) cell lines, we previously characterized a subpopulation of mesenchymal-like cells displaying phenotypic plasticity and increased resistance to both cytotoxic and targeted agents. These mesenchymal-like (Ecad-lo) cells are separable from epithelial-like (Ecad-hi) cells based on loss of surface E-cadherin and expression of vimentin. Despite their long-term plasticity, both Ecad-lo and Ecad-hi subsets in short-term culture maintained nearly uniform phenotypes after purification. This stability allowed testing of segregated subpopulations for relative sensitivity to the cytotoxic agent cisplatin in comparison to salinomycin, a compound with reported activity against CD44+CD24− stem-like cells in breast carcinomas. Salinomycin showed comparable efficacy against both Ecad-hi and Ecad-lo cells in contrast to cisplatin, which selectively depleted Ecad-hi cells. An in vivo correlate of these mesenchymal-like Ecad-lo cells was identified by immunohistochemical detection of vimentin-positive malignant subsets across a part of direct tumor xenografts (DTXs) of advanced stage SCC patient samples. Cisplatin treatment of mice with established DTXs caused enrichment of vimentin-positive malignant cells in residual tumors, but salinomycin depleted the same subpopulation. These results demonstrate that mesenchymal-like SCC cells, which resist current chemotherapies, respond to a treatment strategy developed against a stem-like subset in breast carcinoma. Further, they provide evidence of mesenchymal-like subsets being well-represented across advanced stage SCCs, suggesting that intrinsic drug resistance in this subpopulation has high clinical relevance.Key words: EMT, squamous cell carcinoma, head and neck cancer, esophageal cancer, chemotherapy resistance, salinomycin, tumor heterogeneity 相似文献