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B7-H1 up-regulation on myeloid dendritic cells significantly suppresses T cell immune function in patients with chronic hepatitis B 总被引:18,自引:0,他引:18
Chen L Zhang Z Chen W Zhang Z Li Y Shi M Zhang J Chen L Wang S Wang FS 《Journal of immunology (Baltimore, Md. : 1950)》2007,178(10):6634-6641
Although dysfunctional dendritic cells contribute to inadequate adaptive immunity in chronic hepatitis B (CHB), underlying molecular mechanisms remain largely undefined. In this study, we examined B7-H1 expression on circulating myeloid dendritic cells (mDCs) in 46 CHB patients, 10 autoimmune hepatitis patients, and 10 healthy subjects as control. We found that B7-H1 expression is significantly up-regulated on circulating mDCs of CHB and autoimmune hepatitis patients compared with healthy individuals. The B7-H1 up-regulation was significantly correlated with an elevation of serum alanine aminotransaminase levels and plasma viral load. In addition, in vitro, both IFN-alpha and IFN-gamma could strongly stimulate mDCs to express B7-H1. More importantly, elevated B7-H1 expression is also closely associated with the suppression of T cell immune function. In vitro blockade of B7-H1 signaling could not only down-regulate IL-10 and up-regulate IL-12 production by mDCs, but also enhance mDC-mediated allostimulatory capacity and cytokine production of T cells. Blockade of B7-H1 signaling could improve hepatitis B c Ag-pulsed monocyte-derived DC-induced IFN-gamma production by autologous hepatitis B virus-specific T cells. These new findings suggested that chronic inflammation may contribute to B7-H1 up-regulation on mDCs in CHB patients, which potentially cause defective hepatitis B virus-specific T cell function and viral persistence. Our findings further support the notion that the blockade of B7-H1 may represent a novel therapeutic approach for this disease. 相似文献
143.
The time course of self-assembly of a hybrid hydrogel system was investigated using dynamic light scattering (DLS) techniques. The self-assembling system consisted of a hydrophilic synthetic N-(2-hydroxypropyl)methacrylamide (HPMA) polymer backbone and a pair of oppositely charged peptide grafts (CCE and CCK). These two distinct pentaheptad peptides were anticipated to act as physical cross-linkers by the formation of antiparallel coiled-coil heterodimers. Equimolar mixture of HPMA graft copolymers CCE-P and CCK-P solutions (where P is the HPMA copolymer backbone) with total concentration from 1.25 to 10 mg/mL were measured at a scattering angle 90 degrees and room temperature. A critical extension of average relaxation time was observed with increasing concentration and incubation time. To reveal the role of coiled-coil grafts in the self-assembly process, a pair of modified random coil peptides, CCEw and CCKy, was designed. The DLS evaluation of HPMA copolymer conjugates (CCEw-P and CCKy-P) at total concentration of 10 mg/mL demonstrated that no association occurred after 28 h of incubation. Moreover, addition of a competing peptide (CCK) or a denaturant (guanidium chloride, GndHCl) to the self-assembled CCE-P/CCK-P hydrogels resulted in partial disassembly or collapse of the hydrogel clusters. These results correlated to changes in the secondary structure of peptides (grafts) as measured by circular dichroism spectroscopy (CD). These investigations supported the hypothesis that the self-assembly of CCE-P/CCK-P into hybrid hydrogels is mediated by the formation of coiled-coil heterodimers. 相似文献
144.
1990-2030年中国主要陆地生态系统碳固定服务时空变化 总被引:4,自引:0,他引:4
以中国森林、草地、湿地等主要陆地生态系统为研究对象,估算了植被和土壤有机碳固定量现状与近20年生态系统碳固定变化量,预测了未来20年3种不同社会经济发展情景下主要陆地生态系统的碳固定潜力,评估了我国主要陆地生态系统碳固定服务的现状、过去变化及未来潜力。结果表明:(1)2010年,中国主要陆地生态系统碳固定总量达17.29PgC,其中植被碳固定量8.70PgC,30cm深度土壤有机碳固定量8.59PgC。其中,森林碳固定量占73.26%,草地占21.55%,湿地占5.18%。(2)1990-2000年,我国主要陆地生态系统碳固定总量减少了2.15%,其中森林、草地和湿地分别减少了1.12%、0.97%、20.19%。2000-2010年,碳固定总量增加了2.92%,其中森林增加了3.72%,草地和湿地分别减少了0.62%和5.59%。(3)前、后两个10年相比,碳固定总量从轻微下降转变为轻微上升趋势。其中,森林碳固定量从下降趋势转变为上升趋势,说明生态工程成效明显。草地碳固定量处于基本持衡态势,碳固定减少量和减少比例有所下降,湿地碳固定量的下降趋势亦有所缓解,说明草地退化、湿地破坏趋势有所遏制,但仍需要重点关注。(4)至2030年,3种社会经济发展情景下,我国主要陆地生态系统碳固定总量将呈现较明显的上升态势,增量可达430.11-498.06TgC,增加比例5.15-5.97%,以森林碳固定量增加为主,而草地碳固定服务呈现微弱减少态势。 相似文献
145.
利用RT-PCR和RACE方法,从我国珍稀植物金花茶(Camellia nitidissima)花瓣中获得了查尔酮合成酶(chalcone synthase,CHS)基因的cDNA全长,命名为Cn-CHS,GenBank登录号HQ269804.碱基序列分析表明,Cn-CHS全长1 454bp,包含77 bp的5'非翻译区、207 bp的3'非翻译区和一个长为1 170 bp编码389个氨基酸的开放阅读框.氨基酸序列分析显示该基因编码的蛋白具有CHS家族保守存在的所有功能活性位点和特征性多肽序列.氨基酸序列比对分析表明,CnCHS与蔷薇科、杜鹃花科、茄科等植物的CHS相似性都在92%以上;与山茶科山茶属物种山茶(C.japonica)CHS完全一致;与茶(C.sinensis)CHS相似性达99%,有5个氨基酸位点存在差异,其中包括一个功能性位点. 相似文献
146.
Shujun Nie Bo Wang Haiping Ding Haijian Lin Li Zhang Qigui Li Yujiao Wang Bin Zhang Anping Liang Qi Zheng Hui Wang Huayang Lv Kun Zhu Minghui Jia Xiaotong Wang Jiyuan Du Runtai Zhao Zhenzhen Jiang Caina Xia Zhenghao Qiao Xiaohu Li Boyan Liu Hongbo Zhu Rong An Yucui Li Qian Jiang Benfang Chen Hongkai Zhang Dening Wang Changxiao Tang Yang Yuan Jie Dai Jing Zhan Weiqiang He Xuebo Wang Jian Shi Bin Wang Min Gong Xiujing He Peng Li Li Huang Hui Li Chao Pan Hong Huang Guangsheng Yuan Hai Lan Yongxin Nie Xinzheng Li Xiangyu Zhao Xiansheng Zhang Guangtang Pan Qingyu Wu Fang Xu Zhiming Zhang 《The Plant journal : for cell and molecular biology》2021,108(1):40-54
Maize is an important crop worldwide, as well as a valuable model with vast genetic diversity. Accurate genome and annotation information for a wide range of inbred lines would provide valuable resources for crop improvement and pan-genome characterization. In this study, we generated a high-quality de novo genome assembly (contig N50 of 15.43 Mb) of the Chinese elite inbred line RP125 using Nanopore long-read sequencing and Hi-C scaffolding, which yield highly contiguous, chromosome-length scaffolds. Global comparison of the RP125 genome with those of B73, W22, and Mo17 revealed a large number of structural variations. To create new germplasm for maize research and crop improvement, we carried out an EMS mutagenesis screen on RP125. In total, we obtained 5818 independent M2 families, with 946 mutants showing heritable phenotypes. Taking advantage of the high-quality RP125 genome, we successfully cloned 10 mutants from the EMS library, including the novel kernel mutant qk1 (quekou: “missing a small part” in Chinese), which exhibited partial loss of endosperm and a starch accumulation defect. QK1 encodes a predicted metal tolerance protein, which is specifically required for Fe transport. Increased accumulation of Fe and reactive oxygen species as well as ferroptosis-like cell death were detected in qk1 endosperm. Our study provides the community with a high-quality genome sequence and a large collection of mutant germplasm. 相似文献
147.
Most existing statistical methods developed for calling single nucleotide polymorphisms (SNPs) using next-generation sequencing (NGS) data are based on Bayesian frameworks, and there does not exist any SNP caller that produces p-values for calling SNPs in a frequentist framework. To fill in this gap, we develop a new method MAFsnp, a Multiple-sample based Accurate and Flexible algorithm for calling SNPs with NGS data. MAFsnp is based on an estimated likelihood ratio test (eLRT) statistic. In practical situation, the involved parameter is very close to the boundary of the parametric space, so the standard large sample property is not suitable to evaluate the finite-sample distribution of the eLRT statistic. Observing that the distribution of the test statistic is a mixture of zero and a continuous part, we propose to model the test statistic with a novel two-parameter mixture distribution. Once the parameters in the mixture distribution are estimated, p-values can be easily calculated for detecting SNPs, and the multiple-testing corrected p-values can be used to control false discovery rate (FDR) at any pre-specified level. With simulated data, MAFsnp is shown to have much better control of FDR than the existing SNP callers. Through the application to two real datasets, MAFsnp is also shown to outperform the existing SNP callers in terms of calling accuracy. An R package “MAFsnp” implementing the new SNP caller is freely available at http://homepage.fudan.edu.cn/zhangh/softwares/. 相似文献
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150.
Daewon Kim Jiyuan Yang Fangwei Gu Sungjin Park Jonathon Combs Alexander Adams Heather B Mayes Su Jeong Jeon Jeong Dong Bahk Erik Nielsen 《Plant physiology》2021,185(2):405
In plants, root hairs undergo a highly polarized form of cell expansion called tip-growth, in which cell wall deposition is restricted to the root hair apex. In order to identify essential cellular components that might have been missed in earlier genetic screens, we identified conditional temperature-sensitive (ts) root hair mutants by ethyl methanesulfonate mutagenesis in Arabidopsis thaliana. Here, we describe one of these mutants, feronia-temperature sensitive (fer-ts). Mutant fer-ts seedlings were unaffected at normal temperatures (20°C), but failed to form root hairs at elevated temperatures (30°C). Map based-cloning and whole-genome sequencing revealed that fer-ts resulted from a G41S substitution in the extracellular domain of FERONIA (FER). A functional fluorescent fusion of FER containing the fer-ts mutation localized to plasma membranes, but was subject to enhanced protein turnover at elevated temperatures. While tip-growth was rapidly inhibited by addition of rapid alkalinization factor 1 (RALF1) peptides in both wild-type and fer-ts mutants at normal temperatures, root elongation of fer-ts seedlings was resistant to added RALF1 peptide at elevated temperatures. Additionally, at elevated temperatures fer-ts seedlings displayed altered reactive oxygen species (ROS) accumulation upon auxin treatment and phenocopied constitutive fer mutant responses to a variety of plant hormone treatments. Molecular modeling and sequence comparison with other Catharanthus roseus receptor-like kinase 1L (CrRLK1L) receptor family members revealed that the mutated glycine in fer-ts is highly conserved, but is not located within the recently characterized RALF23 and LORELI-LIKE-GLYCOPROTEIN 2 binding domains, perhaps suggesting that fer-ts phenotypes may not be directly due to loss of binding to RALF1 peptides.A new, temperature-sensitive allele of FERONIA rapidly inhibits FER signaling and root hair tip-growth at elevated temperatures. 相似文献