全文获取类型
收费全文 | 88篇 |
免费 | 4篇 |
出版年
2021年 | 1篇 |
2018年 | 1篇 |
2016年 | 3篇 |
2015年 | 5篇 |
2014年 | 4篇 |
2013年 | 8篇 |
2012年 | 11篇 |
2011年 | 6篇 |
2010年 | 5篇 |
2008年 | 6篇 |
2007年 | 4篇 |
2006年 | 4篇 |
2005年 | 6篇 |
2004年 | 1篇 |
2003年 | 6篇 |
2002年 | 2篇 |
2001年 | 1篇 |
2000年 | 1篇 |
1999年 | 1篇 |
1998年 | 1篇 |
1997年 | 2篇 |
1996年 | 1篇 |
1992年 | 1篇 |
1991年 | 1篇 |
1989年 | 1篇 |
1988年 | 2篇 |
1987年 | 1篇 |
1986年 | 1篇 |
1985年 | 1篇 |
1983年 | 1篇 |
1976年 | 1篇 |
1973年 | 1篇 |
1970年 | 1篇 |
排序方式: 共有92条查询结果,搜索用时 62 毫秒
41.
Jenny Schlesinger Martje Tönjes Markus Schueler Qin Zhang Ilona Dunkel Silke R. Sperling 《Methods (San Diego, Calif.)》2010,50(4):S19-S22
Quantitative real-time PCR (qPCR) is a frequently used, sensitive and accurate method to study gene expression profiles. However, its throughput was so far limited for routine laboratories to 384 reactions per run based on the limitations of the available instruments. Recently, the LightCycler® 1536 Instrument was launched providing a high-throughput solution for qPCR with the analysis of 1536 reactions in approximately 45 min. We assessed the accuracy and sensitivity of this novel technology for the analysis of gene expression profiles in combination with the Innovadyne? Nanodrop? Express pipetting robot. We compared expression profiles obtained for 42 genes in 71 samples between the Universal ProbeLibrary and the LightCycler® 1536 Instrument and SYBR Green I and the ABI PRISM 7900HT system. We found that the results were highly reproducible between both systems. Beside the higher throughput, the advantage of the LightCycler® 1536 Instrument was the reduced consumption of reagents and sample material. 相似文献
42.
Corin L. Dorfmeier Andrew G. Lytle Amber L. Dunkel Anthony Gatt James P. McGettigan 《Journal of virology》2012,86(21):11533-11540
A major goal in rabies virus (RV) research is to develop a single-dose postexposure prophylaxis (PEP) that would simplify vaccination protocols, reduce costs associated with rabies prevention in humans, and save lives. Live replication-deficient RV-based vaccines are emerging as promising single-dose vaccines to replace currently licensed inactivated RV-based vaccines. Nonetheless, little is known about how effective B cells develop in response to live RV-based vaccination. Understanding this fundamental property of rabies immunology may help in developing a single-dose RV vaccine. Typically, vaccines induce B cells secreting high-affinity, class-switched antibodies during germinal center (GC) reactions; however, there is a lag time between vaccination and the generation of GC B cells. In this report, we show that RV-specific antibodies are detected in mice immunized with live but not inactivated RV-based vaccines before B cells displaying a GC B cell phenotype (B220+GL7hiCD95hi) are formed, indicating a potential role for T cell-independent and early extrafollicular T cell-dependent antibody responses in the protection against RV infection. Using two mouse models of CD4+ T cell deficiency, we show that B cells secreting virus-neutralizing antibodies (VNAs) are induced via T cell-independent mechanisms within 4 days postimmunization with a replication-deficient RV-based vaccine. Importantly, mice that are completely devoid of T cells (B6.129P2-Tcrβtm1Mom
Tcrδtm1Mom/J) show protection against pathogenic challenge shortly after immunization with a live replication-deficient RV-based vaccine. We show that vaccines that can exploit early pathways of B cell activation and development may hold the key for the development of a single-dose RV vaccine wherein the rapid induction of VNA is critical. 相似文献
43.
44.
The progesterone-binding protein uteroglobin has been expressed in Escherichia coli in an unfused, soluble form. Like mature uteroglobin from rabbit endometrium (UG), the E.coli produced uteroglobin (UG1) dimerizes in vitro, forms an antiparallel dimer with Cys3-Cys69' and Cys69-Cys3' disulfide bonds and binds progesterone under reducing conditions. In order to analyze the dimerization and the reduction dependence of progesterone binding in more detail, we separately replaced cysteine 3 and cysteine 69 by serines. Under reducing conditions, both uteroglobin variants (UG1-3Ser and UG1-69Ser) bind progesterone with the same affinity as the wild-type suggesting that both cysteine residues are not directly involved in progesterone binding. In contrast to the wild-type protein, both cysteine variants also bind progesterone with high affinity in the absence of reducing agents. In addition, UG1-3Ser and UG1-69Ser both form covalently linked homodimers. Thus, unnatural Cys69-69' and Cys3-3' disulfide bonds exist in UG1-3Ser and UG1-69Ser, respectively. These data together with computer models based on X-ray diffraction data strongly support the idea that progesterone reaches its binding site located in an internal hydrophobic cavity via a hydrophobic tunnel along helices 1 and 4. Under non-reducing conditions the tunnel is closed by two disulfide bridges (Cys3-Cys69' and Cys69-Cys3') that lie in the most flexible region of the dimer. Reduction or replacement of a cysteine residue enables conformational changes that open the channel allowing progesterone to enter. 相似文献
45.
For DNA single molecule sequencing, the complete detection of all dye-labeled monomers which are cleaved off during the sequencing reaction is an essential requirement. In this work we address the feasibility of single molecule detection in microstructures with a confocal multi element set-up. We present statistical data on single molecule recognition and explain a refined data evaluation technique for single molecule burst analysis. From these data the signal-to-noise ratio in microstructures is evaluated as well as the overall detection efficiency. So far, detection efficiencies of single molecule events of up to 60% have been shown in microstructures. 相似文献
46.
47.
48.
Y. Pierre Gobin Ira J. Dunkel Brian P. Marr Jasmine H. Francis Scott E. Brodie David H. Abramson 《PloS one》2012,7(9)
Background
Intra-arterial (IA) chemotherapy has more risks of procedural complications in neonates and young infants. For these reasons, we have developed a strategy of bridge intravenous single agent chemotherapy to postpone IA chemotherapy in these childrenProcedure
Neonates and young infants with retinoblastoma who required chemotherapy were treated with systemic carboplatin chemotherapy (18.7 mg/kg IV every 3–4 weeks) until they reached the age of 3 months and a weight of 6 Kg. If necessary, IA chemotherapy was subsequently performed at 4 weeks intervals. Efficacy was judged by tumor regression on ophthalmological examination. Retinal toxicity was judged by electroretinography.Results
Eleven children (19 eyes) were treated. All patients are alive and no patient has developed metastatic disease or second malignancies (mean follow-up 27 months, range 9–46 months). Intravenous carboplatin (median 2 cycles, range 1–5) combined with cryotherapy and laser was given to all children. This was effective for five eyes, which did not require IA chemotherapy. IA chemotherapy was administered to 14 eyes (median 3.5 cycles per eye, range 1 to 6). No radiation therapy was required. The Kaplan Meier estimate of ocular radiation-free survival was 94.7% at one year (95% confidence interval 68.1–99.2%). One eye was enucleated due to tumor progression. ERG showed no deterioration of retinal function.Conclusion
Bridge IV-IA chemotherapy was feasible and safe, and is a promising strategy to treat retinoblastoma in neonates and young infants. 相似文献49.
Saskia Preissner Mathias Dunkel Michael F. Hoffmann Sarah C. Preissner Nikolai Genov Wen Wei Rong Robert Preissner Karlheinz Seeger 《PloS one》2012,7(12)
Background
In general, drug metabolism has to be considered to avoid adverse effects and ineffective therapy. In particular, chemotherapeutic drug cocktails strain drug metabolizing enzymes especially the cytochrome P450 family (CYP). Furthermore, a number of important chemotherapeutic drugs such as cyclophosphamide, ifosfamide, tamoxifen or procarbazine are administered as prodrugs and have to be activated by CYP. Therefore, the genetic variability of these enzymes should be taken into account to design appropriate therapeutic regimens to avoid inadequate drug administration, toxicity and inefficiency.Objective
The aim of this work was to find drug interactions and to avoid side effects or ineffective therapy in chemotherapy.Data sources and methods
Information on drug administration in the therapy of leukemia and their drug metabolism was collected from scientific literature and various web resources. We carried out an automated textmining approach. Abstracts of PubMed were filtered for relevant articles using specific keywords. Abstracts were automatically screened for antineoplastic drugs and their synonyms in combination with a set of human CYPs in title or abstract.Results
We present a comprehensive analysis of over 100 common cancer treatment regimens regarding drug-drug interactions and present alternatives avoiding CYP overload. Typical concomitant medication, e.g. antiemetics or antibiotics is a preferred subject to improvement. A webtool, which allows drug cocktail optimization was developed and is publicly available on http://bioinformatics.charite.de/chemotherapy. 相似文献50.