全文获取类型
收费全文 | 415篇 |
免费 | 35篇 |
专业分类
450篇 |
出版年
2023年 | 4篇 |
2022年 | 15篇 |
2021年 | 19篇 |
2020年 | 10篇 |
2019年 | 18篇 |
2018年 | 17篇 |
2017年 | 14篇 |
2016年 | 15篇 |
2015年 | 16篇 |
2014年 | 20篇 |
2013年 | 24篇 |
2012年 | 34篇 |
2011年 | 36篇 |
2010年 | 22篇 |
2009年 | 12篇 |
2008年 | 17篇 |
2007年 | 19篇 |
2006年 | 15篇 |
2005年 | 8篇 |
2004年 | 13篇 |
2003年 | 14篇 |
2002年 | 10篇 |
2001年 | 8篇 |
2000年 | 4篇 |
1999年 | 6篇 |
1998年 | 4篇 |
1997年 | 2篇 |
1992年 | 3篇 |
1991年 | 4篇 |
1990年 | 3篇 |
1989年 | 2篇 |
1987年 | 1篇 |
1986年 | 5篇 |
1985年 | 1篇 |
1984年 | 4篇 |
1983年 | 2篇 |
1982年 | 2篇 |
1981年 | 3篇 |
1978年 | 3篇 |
1976年 | 3篇 |
1972年 | 2篇 |
1968年 | 2篇 |
1953年 | 1篇 |
1944年 | 1篇 |
1933年 | 1篇 |
1928年 | 2篇 |
1927年 | 2篇 |
1923年 | 1篇 |
1920年 | 1篇 |
1909年 | 1篇 |
排序方式: 共有450条查询结果,搜索用时 15 毫秒
21.
22.
Mallikaratchy PR Ruggiero A Gardner JR Kuryavyi V Maguire WF Heaney ML McDevitt MR Patel DJ Scheinberg DA 《Nucleic acids research》2011,39(6):2458-2469
Long-term survival still eludes most patients with leukemia and non-Hodgkin's lymphoma. No approved therapies target the hallmark of the B cell, its mIgM, also known as the B-cell receptor (BCR). Aptamers are small oligonucleotides that can specifically bind to a wide range of target molecules and offer some advantages over antibodies as therapeutic agents. Here, we report the rational engineering of aptamer TD05 into multimeric forms reactive with the BCR that may be useful in biomedical applications. Systematic truncation of TD05 coupled with modification with locked nucleic acids (LNA) increased conformational stability and nuclease resistance. Trimeric and tetrameric versions with optimized polyethyleneglycol (PEG) linker lengths exhibited high avidity at physiological temperatures both in vitro and in vivo. Competition and protease studies showed that the multimeric, optimized aptamer bound to membrane-associated human mIgM, but not with soluble IgM in plasma, allowing the possibility of targeting leukemias and lymphomas in vivo. The B-cell specificity of the multivalent aptamer was confirmed on lymphoma cell lines and fresh clinical leukemia samples. The chemically engineered aptamers, with significantly improved kinetic and biochemical features, unique specificity and desirable pharmacological properties, may be useful in biomedical applications. 相似文献
23.
24.
25.
Adnan O. Abu-Yousif Imran Rizvi Conor L. Evans Jonathan P. Celli Tayyaba Hasan 《Journal of visualized experiments : JoVE》2009,(34)
Increasing evidence suggests that culturing cancer cells in three dimensions more accurately recapitulates the complexity of tumor biology. Many of these models utilize reconstituted basement membrane derived from animals which contain a variable amount of growth factors and cytokines that can influence the growth of these cell culture models. Here, we describe in detail the preparation and use of PuraMatrix, a commercially available self assembling peptide gel that is devoid of animal-derived material and pathogens to encapsulate and propagate the ovarian cancer cell line, OVCAR-5. We begin by describing how to prepare the PuraMatrix prior to use. Next, we demonstrate how to properly mix the PuraMatrix and cell suspension to encapsulate the cells in the hydrogel. Upon the addition of cell culture media or injection into a physiological environment, the peptide component of PuraMatrix rapidly self assembles into a 3D hydrogel that exhibits a nanometer scale fibrous structure with an average pore size of 5-200 nm1. In addition, we demonstrate how to propagate cultures grown in encapsulated PuraMatrix. When encapsulated in PuraMatrix, OVCAR-5 cells assemble into three dimensional acinar structures that more closely resemble the morphology of micrometastatic nodules observed in the clinic than monolayer in vitro models. Using confocal microscopy we illustrate the appearance of representative OVCAR-5 cells encapsulated in PuraMatrix on day 1, 3, 5, and 7 post plating. The use of PuraMatrix to culture cancer cells should improve our understanding of the disease and allow us to assess treatment response in more clinically predictive model systems.Download video file.(85M, mp4) 相似文献
26.
Evonne Low Sean R. Mathieson Nathan J. Stevenson Vicki Livingstone C. Anthony Ryan Conor O. Bogue Janet M. Rennie Geraldine B. Boylan 《PloS one》2014,9(7)
Background
Stroke is the second most common cause of seizures in term neonates and is associated with abnormal long-term neurodevelopmental outcome in some cases.Objective
To aid diagnosis earlier in the postnatal period, our aim was to describe the characteristic EEG patterns in term neonates with perinatal arterial ischaemic stroke (PAIS) seizures.Design
Retrospective observational study.Patients
Neonates >37 weeks born between 2003 and 2011 in two hospitals.Method
Continuous multichannel video-EEG was used to analyze the background patterns and characteristics of seizures. Each EEG was assessed for continuity, symmetry, characteristic features and sleep cycling; morphology of electrographic seizures was also examined. Each seizure was categorized as electrographic-only or electroclinical; the percentage of seizure events for each seizure type was also summarized.Results
Nine neonates with PAIS seizures and EEG monitoring were identified. While EEG continuity was present in all cases, the background pattern showed suppression over the infarcted side; this was quite marked (>50% amplitude reduction) when the lesion was large. Characteristic unilateral bursts of theta activity with sharp or spike waves intermixed were seen in all cases. Sleep cycling was generally present but was more disturbed over the infarcted side. Seizures demonstrated a characteristic pattern; focal sharp waves/spike-polyspikes were seen at frequency of 1–2 Hz and phase reversal over the central region was common. Electrographic-only seizure events were more frequent compared to electroclinical seizure events (78 vs 22%).Conclusions
Focal electrographic and electroclinical seizures with ipsilateral suppression of the background activity and focal sharp waves are strong indicators of PAIS. Approximately 80% of seizure events were the result of clinically unsuspected seizures in neonates with PAIS. Prolonged and continuous multichannel video-EEG monitoring is advocated for adequate seizure surveillance. 相似文献27.
Identification of a new segment involved in cagA 3' region variation of Helicobacter pylori 总被引:2,自引:0,他引:2
Dong Q O'Sullivan M Hall W Herra C Kean C O'Morain C Buckley M 《FEMS immunology and medical microbiology》2002,33(1):51-55
The cagA 3' region shows marked variation among Helicobacter pylori strains. Two segments of 102 bp and 57 bp are reportedly responsible for this variation. We analysed the cagA 3' region in 70 H. pylori strains using polymerase chain reaction and sequencing. We found that another segment, namely beta segment, was also involved in the variation of this region. The beta segment was 105 bp long and located between the aforementioned two segments. Six genotypes were identified based on the structure of the cagA 3' region. No relationship was found between these genotypes and the clinical outcomes or vacA genotypes. The numbers of tyrosine phosphorylation sites within the cagA 3' region varied among strains, but this was not related to the cagA genotypes. Our data suggest that the cagA 3' region is significantly variable. It appears that the variation of the cagA 3' region might contribute to the modification of virulence. 相似文献
28.
29.
Lawrence R. Heaney 《Oecologia》1984,61(1):11-17
Summary A rich mammalian fauna is found on islands that lie on the Sunda Shelf, a continental shelf extending from Vietnam to Borneo and Java that was periodically exposed as dry land during the Pleistocene. The correlation between log of island area and number of species is high (r
2=0.94); the slope of the curve is moderate (z=0.235). Distance from small islands to source areas (=Borneo, Sumatra, and the Malay Peninsula) does not appear to affect species richness, nor does depth of water to source area (a measure of isolation time). A species-area curve for forest reserves of varying sizes on the Malay Peninsula has a low slope (z=0.104); comparison of the mainlaind and island curves indicates that decreasing island area is strongly correlated with increased extinction. Extinction has left reduced but ecologically balanced sets of species on all islands, except that carnivores are under-represented on all but the largest islands. Initial body size and rarity appear to play a significant role in determining the probability of extinction of individual species. 相似文献
30.