全文获取类型
收费全文 | 297篇 |
免费 | 12篇 |
专业分类
309篇 |
出版年
2022年 | 2篇 |
2021年 | 2篇 |
2020年 | 4篇 |
2019年 | 2篇 |
2018年 | 8篇 |
2017年 | 4篇 |
2016年 | 19篇 |
2015年 | 13篇 |
2014年 | 20篇 |
2013年 | 12篇 |
2012年 | 31篇 |
2011年 | 25篇 |
2010年 | 15篇 |
2009年 | 25篇 |
2008年 | 26篇 |
2007年 | 22篇 |
2006年 | 13篇 |
2005年 | 16篇 |
2004年 | 16篇 |
2003年 | 11篇 |
2002年 | 5篇 |
2001年 | 5篇 |
2000年 | 4篇 |
1999年 | 1篇 |
1998年 | 1篇 |
1996年 | 2篇 |
1992年 | 2篇 |
1989年 | 1篇 |
1985年 | 1篇 |
1975年 | 1篇 |
排序方式: 共有309条查询结果,搜索用时 0 毫秒
101.
102.
103.
104.
Red to red - the marine bacterium Hahella chejuensis and its product prodigiosin for mitigation of harmful algal blooms 总被引:2,自引:0,他引:2
Kim D Kim JF Yim JH Kwon SK Lee CH Lee HK 《Journal of microbiology and biotechnology》2008,18(10):1621-1629
Harmful algal blooms (HABs), commonly called red tides, are caused by some toxic phytoplanktons, and have made massive economic losses as well as marine environmental disturbances. As an effective and environment-friendly strategy to control HAB outbreaks, biological methods using marine bacteria capable of killing the harmful algae or algicidal extracellular compounds from them have been given attention. A new member of the gamma-Proteobacteria, Hahella chejuensis KCTC 2396, was originally isolated from the Korean seashore for its ability to secrete industrially useful polysaccharides, and was characterized to produce a red pigment. This pigment later was identified as an alkaloid compound, prodigiosin. During the past several decades, prodigiosin has been extensively studied for its medical potential as immunosuppressants and antitumor agents, owing to its antibiotic and cytotoxic activities. The lytic activity of this marvelous molecule against Cochlodinium polykrikoides cells at very low concentrations (1 ppb) was serendipitously detected, making H. chejuensis a strong candidate among the biological agents for HAB control. This review provides a brief overview of algicidal marine bacteria and their products, and describes in detail the algicidal characteristics, biosynthetic process, and genetic regulation of prodigiosin as a model among the compounds active against red-tide organisms from the biochemical and genetic viewpoints. 相似文献
105.
Taek Lee Chul-Hyun Cho Woon Ryoung Kim Joung Ho Moon Soojin Kim 《Chronobiology international》2020,37(7):993-1001
ABSTRACT Considering the effects of circadian misalignment on human pathophysiology and behavior, it is important to be able to detect an individual’s endogenous circadian time. We developed an endogenous Clock Estimation Model (eCEM) based on a machine learning process using the expression of 10 circadian genes. Hair follicle cells were collected from 18 healthy subjects at 08:00, 11:00, 15:00, 19:00, and 23:00 h for two consecutive days, and the expression patterns of 10 circadian genes were obtained. The eCEM was designed using the inverse form of the circadian gene rhythm function (i.e., Circadian Time = F(gene)), and the accuracy of eCEM was evaluated by leave-one-out cross-validation (LOOCV). As a result, six genes (PER1, PER3, CLOCK, CRY2, NPAS2, and NR1D2) were selected as the best model, and the error range between actual and predicted time was 3.24 h. The eCEM is simple and applicable in that a single time-point sampling of hair follicle cells at any time of the day is sufficient to estimate the endogenous circadian time. 相似文献
106.
Gus expression was determined for 19 lines of embryogenic Gladiolus callus that contained the 35S-bar-uidA-nos fusion gene and for 21 callus lines that had been cobombarded with the 35S-bar-nos and 35S-uidA-nos plasmid DNAs. These lines were selected for analysis because they grew vigorously on Murashige and Skoog’s medium supplemented
with 6 mg l−1 phosphinothricin. All 19 lines that contained the 35S-bar-uidA-nos fusion gene expressed gus compared to only 15 (71%) of the lines that had been cobombarded as determined by enzyme assay.
The level of gus expression was significantly higher the first year for 12 callus lines containing the bar-uidA fusion gene as compared to 2 years later in culture. Southern hybridization confirmed integration of the uidA gene in all callus lines that had been bombarded with the 35S-bar-uidA-nos fusion gene. Two of the callus lines that had been cobombarded lacked the uidA gene, and another cobombarded line that did not express gus contained a truncated uidA gene. Two callus lines resulting from cobombardment showed gus expression in only a few cells indicating that gus expression
was not completely silenced in these lines. Gus expression could not be reversed using 5-azacytidine in these two low-expressing
lines, and Southern hybridization supported that methylation of the genomic DNA had not occurred. Average levels of gus expression
were significantly higher, 8.9× , in cells with the 35S-bar-uidA-nos fusion gene compared to the cobombarded callus lines indicating the advantage of using a bar-uidA fusion gene for obtaining higher levels of gus expression in Gladiolus. 相似文献
107.
Su-Hyun Kim So-Young Huh Jae-Won Hyun In Hye Jeong Sang Hyun Lee AeRan Joung Ho Jin Kim 《PloS one》2014,9(9)
Brain involvement is commonly seen in patients with neuromyelitis optica spectrum disorder (NMOSD). However, little is known about the chronic changes of acute brain lesions on MRI over time. Here, our objective was to evaluate how acute brain MRI lesions in NMOSD changed on follow-up MRI. We reviewed the MRIs of 63 patients with NMOSD who had acute brain lesions and follow-up MRI over an interval of at least 3 months. Of the 211 acute brain lesions, 24% of lesions disappeared completely on T2-weighed images (WI) and a decrease in size ≥50% on T2-WI was observed in 58% of lesions on follow-up MRI. However, 47% of lesions revealed focal T1-hypointensity and, in particular, 18% showed focal cystic changes. Cystic changes were observed most commonly in corticospinal tract and corpus callosal lesions whereas the vast majority of lesions in the cerebellum, basal ganglia and temporal white matter resolved completely. MRI remission on T2-WI occurred in 82% of lesions, while approximately half of the lesions presented foci of T1-hypointensity, which may be considered a severe tissue injury over time. The extent of brain injury following an acute brain lesion in NMOSD may depend on the location of the lesion. 相似文献
108.
Jun Choul Lee Byung Kil Park Sorim Choung Ji Min Kim Kyong Hye Joung Ju Hee Lee Koon Soon Kim Hyun Jin Kim Jae-Wook Jeong Sang Dal Rhee Bon Jeong Ku 《PloS one》2014,9(12)
Mitogen-inducible gene 6 (Mig-6) is a negative feedback inhibitor of epidermal growth factor receptor (EGFR) signaling. We previously found that Mig-6 plays a critical role in the regulation of cholesterol homeostasis and in bile acid synthesis. In this study, we investigated the effects of EGFR inhibition to identify a potential new treatment target for hypercholesterolemia. We used a mouse model with conditional ablation of the Mig-6 gene in the liver (Albcre/+Mig-6f/f; Mig-6d/d) to effectively investigate the role of Mig-6 in the regulation of liver function. Mig-6d/d mice were treated with either the EGFR inhibitor gefitinib or statin for 6 weeks after administration of a high-fat or standard diet. We then compared lipid profiles and other parameters among each group of mice. After a high-fat diet, Mig-6d/d mice showed elevated serum levels of total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides and glucose, characteristics resembling hypercholesterolemia in diabetic patients. We observed decreases in serum levels of lipids and glucose in high-fat-diet-fed Mig-6d/d mice after 6 weeks of treatment with gefitinib or statin. Furthermore gefitinib-treated mice showed significantly greater decreases in serum levels of total, HDL and LDL cholesterol compared with statin-treated mice. Taken together, these results suggest that EGFR inhibition is effective for the treatment of hypercholesterolemia in high-fat-diet-fed Mig-6d/d mice, and our findings provide new insights into the development of possible treatment targets for hypercholesterolemia via modulation of EGFR inhibition. 相似文献
109.
110.
Engineered zinc finger nickases induce homology-directed repair with reduced mutagenic effects 总被引:1,自引:0,他引:1
Ramirez CL Certo MT Mussolino C Goodwin MJ Cradick TJ McCaffrey AP Cathomen T Scharenberg AM Joung JK 《Nucleic acids research》2012,40(12):5560-5568
Engineered zinc finger nucleases (ZFNs) induce DNA double-strand breaks at specific recognition sequences and can promote efficient introduction of desired insertions, deletions or substitutions at or near the cut site via homology-directed repair (HDR) with a double- and/or single-stranded donor DNA template. However, mutagenic events caused by error-prone non-homologous end-joining (NHEJ)-mediated repair are introduced with equal or higher frequency at the nuclease cleavage site. Furthermore, unintended mutations can also result from NHEJ-mediated repair of off-target nuclease cleavage sites. Here, we describe a simple and general method for converting engineered ZFNs into zinc finger nickases (ZFNickases) by inactivating the catalytic activity of one monomer in a ZFN dimer. ZFNickases show robust strand-specific nicking activity in vitro. In addition, we demonstrate that ZFNickases can stimulate HDR at their nicking site in human cells, albeit at a lower frequency than by the ZFNs from which they were derived. Finally, we find that ZFNickases appear to induce greatly reduced levels of mutagenic NHEJ at their target nicking site. ZFNickases thus provide a promising means for inducing HDR-mediated gene modifications while reducing unwanted mutagenesis caused by error-prone NHEJ. 相似文献