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排序方式: 共有268条查询结果,搜索用时 500 毫秒
171.
Liwei Zhang Dangsheng Huang Dong Shen Chunhong Zhang Yongjiang Ma Sara A. Babcock Bingyang Chen Jun Ren 《Life sciences》2014
Aims
Accumulation of advanced glycation endproduct (AGE) contributes to diabetic complication including diabetic cardiomyopathy although the precise underlying mechanism still remains elusive. Recent evidence depicted a pivotal role of protein kinase C (PKC) in diabetic complications. To this end, this study was designed to examine if PKCβII contributes to AGE-induced cardiomyocyte contractile and intracellular Ca2 + aberrations.Main methods
Adult rat cardiomyocytes were incubated with methylglyoxal-AGE (MG-AGE) in the absence or presence of the PKCβII inhibitor LY333531 for 12 h. Contractile and intracellular Ca2 + properties were assessed using an IonOptix system including peak shortening (PS), maximal velocity of shortening/relengthening (± dL/dt), time-to-PS (TPS), time-to-90% relengthening (TR90), rise in intracellular Ca2 + Fura-2 fluorescence intensity and intracellular Ca2 + decay. Oxidative stress, O2− production and mitochondrial integrity were examined using TBARS, fluorescence imaging, aconitase activity and Western blotting.Key findings
MG-AGE compromised contractile and intracellular Ca2 + properties including reduced PS, ± dL/dt, prolonged TPS and TR90, decreased electrically stimulated rise in intracellular Ca2 + and delayed intracellular Ca2 + clearance, the effects of which were ablated by the PKCβII inhibitor LY333531. Inhibition of PKCβII rescued MG-AGE-induced oxidative stress, O2− generation, cell death, apoptosis and mitochondrial injury (reduced aconitase activity, UCP-2 and PGC-1α). In vitro studies revealed that PKCβII inhibition-induced beneficial effects were replicated by the NADPH oxidase inhibitor apocynin and were mitigated by the mitochondrial uncoupler FCCP.Significance
These findings implicated the therapeutic potential of specific inhibition of PKCβII isoform in the management of AGE accumulation-induced myopathic anomalies. 相似文献172.
Here, we describe peptide aggregation, which is also known as enzymatic protein resynthesis. Whey protein hydrolysate (WPH) is the starting material for assembling peptides. Analyses of the involved amino acids, intrinsic fluorescence, fluorescence phase diagram, secondary structure, turbidity, and surface hydrophobicity were performed to investigate the reaction process. The aggregation mechanism consists of two parts: 1) formation and 2) aggregation of the building blocks that form the ordered secondary β-sheet structure. Constructing the building blocks requires at least one intermediate state, which is formed after 0.5 hours. Non-synergistic changes in the secondary and tertiary structures then allow the intermediate state to emerge. 相似文献
173.
Xingsheng Hu Li Zhang Yuankai Shi Caicun Zhou Xiaoqing Liu Dong Wang Yong Song Qiang Li Jifeng Feng Shukui Qin Nong Xv Jianying Zhou Li Zhang Chunhong Hu Shucai Zhang Rongcheng Luo Jie Wang Fenlai Tan Yinxiang Wang Lieming Ding Yan Sun 《PloS one》2015,10(11)
Background
Icotinib is a small molecule targeting epidermal growth factor receptor tyrosine kinase, which shows non-inferior efficacy and better safety comparing to gefitinib in previous phase III trial. The present study was designed to further evaluate the efficacy and safety of icotinib in patients with advanced non-small-cell lung cancer (NSCLC) previously treated with platinum-based chemotherapy.Methods
Patients with NSCLC progressing after one or two lines of chemotherapy were enrolled to receive oral icotinib (125mg tablet, three times per day). The primary endpoint was progression-free survival. The secondary endpoints included overall survival, objective response rate, time to progression, quality of life and safety.Results
From March 16, 2010 to October 9, 2011, 128 patients from 15 centers nationwide were enrolled, in which 124 patients were available for efficacy evaluation and 127 patients were evaluable for safety. The median progression-free survival and time to progression were 5.0 months (95%CI 2.9–6.6 m) and 5.4 months (95%CI 3.1–7.9 m), respectively. The objective response rate and disease control rate were 25.8% and 67.7% respectively. Median overall survival exceeded 17.6 months (95%CI 14.2 m-NA) according to censored data. Further follow-up of overall survival is ongoing. The most frequent treatment-related adverse events were rash (26%, 33/127), diarrhea (12.6%, 16/127) and elevation of transaminase (15.7%, 20/127).Conclusions
In general, this study showed similar efficacy and numerically better safety when compared with that in ICOGEN trial, further confirming the efficacy and safety of icotinib in treating patients with advanced NSCLC previously treated with chemotherapy.Trial Registration
ClinicalTrials.gov NCT02486354 相似文献174.
Manufacture of Cheddar cheese using probiotic Lactobacillus plantarum K25 and its cholesterol-lowering effects in a mice model 总被引:2,自引:0,他引:2
Li Zhang Xue Zhang Chunhong Liu Changying Li Shengyu Li Tiezhu Li Da Li Yujuan Zhao Zhennai Yang 《World journal of microbiology & biotechnology》2013,29(1):127-135
The probiotic adjunct Lactobacillus plantarum K25 was inoculated into milk to produce probiotic cheese. The effect of Lb. plantarum K25 on cheese composition, microbiological growth and survival during the manufacturing and ripening period, primary and secondary proteolysis during cheese ripening, and the in vivo cholesterol-lowering ability of the probiotic cheese were investigated. The results showed that the use of adjunct Lb. plantarum K25 in Cheddar cheese did not affect the cheese components including moisture, protein, fat, salt content and the pH value of cheese. During the whole ripening period, the probiotic adjunct maintained its viability, suggesting the effectiveness of Cheddar cheese as a vehicle for delivery of probiotic bacteria. No significant differences were observed in water-soluble nitrogen, 70?% ethanol-soluble nitrogen, 5?% phosphotungstic acid-soluble nitrogen, free amino acids and urea-PAGE patterns between the control and probiotic cheeses. Assessment of the in vivo cholesterol-lowering property of cheese with Lb. plantarum K25 showed that the levels of serum total cholesterol, low-density lipoprotein cholesterol and triglycerides decreased significantly, and the level of serum high-density lipoprotein cholesterol increased in mice fed with the probiotic cheese. The results indicated the potential function as a dietary item of the probiotic cheese with Lb. plantarum K25 to reduce the risk of cardiovascular diseases. 相似文献
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177.
Jing Wang Dengpeng Ren Yan Sun Chao Xu Chunhong Wang Rui Cheng Lina Wang Guijun Jia Jinrui Ren Jiuhong Ma Yue Tu Hongming Ji 《Journal of cellular and molecular medicine》2020,24(7):3931-3947
Glioblastoma (GBM) is one of the most common aggressive cancers of the central nervous system in adults with a high mortality rate. Bortezomib is a boronic acid–based potent proteasome inhibitor that has been actively studied for its anti-tumour effects through inhibition of the proteasome. The proteasome is a key component of the ubiquitin-proteasome pathway that is critical for protein homeostasis, regulation of cellular growth, and apoptosis. Overexpression of polo-like kinase 4 (PLK4) is commonly reported in tumour cells and increases their invasive and metastatic abilities. In this study, we established a cell model of PLK4 knockdown and overexpression in LN-18, A172 and LN-229 cells and found that knockdown of PLK4 expression enhanced the anti-tumour effect of bortezomib. We further found that this effect may be mediated by the PTEN/PI3K/AKT/mTOR signalling pathway and that the apoptotic and oxidative stress processes were activated, while the expression of matrix metalloproteinases (MMPs) was down-regulated. Similar phenomenon was observed using in vitro experiments. Thus, we speculate that PLK4 inhibition may be a new therapeutic strategy for GBM. 相似文献
178.
Jing Sun Yanfang Zhang Minhui Wang Qian Guan Xiujia Yang Jin Xia Ou Mingchen Yan Chengrui Wang Yan Zhang Zhi-Hao Li Chunhong Lan Chen Mao Hong-Wei Zhou Bingtao Hao Zhenhai Zhang 《基因组蛋白质组与生物信息学报(英文版)》2020,18(5):516-524
Identification of genetic variants via high-throughput sequencing (HTS) technologies has been essential for both fundamental and clinical studies. However, to what extent the genome sequence composition affects variant calling remains unclear. In this study, we identified 63,897 multi-copy sequences (MCSs) with a minimum length of 300 bp, each of which occurs at least twice in the human genome. The 151,749 genomic loci (multi-copy regions, or MCRs) harboring these MCSs account for 1.98% of the genome and are distributed unevenly across chromosomes. MCRs containing the same MCS tend to be located on the same chromosome. Gene Ontology (GO) analyses revealed that 3800 genes whose UTRs or exons overlap with MCRs are enriched for Golgi-related cellular component terms and various enzymatic activities in the GO biological function category. MCRs are also enriched for loci that are sensitive to neocarzinostatin-induced double-strand breaks. Moreover, genetic variants discovered by genome-wide association studies and recorded in dbSNP are significantly underrepresented in MCRs. Using simulated HTS datasets, we show that false variant discovery rates are significantly higher in MCRs than in other genomic regions. These results suggest that extra caution must be taken when identifying genetic variants in the MCRs via HTS technologies. 相似文献
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180.
Berteroa incana (B. incana), a spring ephemeral species of Brassicaceae, possesses very high photosynthetic capacities at high irradiances. Exploring the mechanism of the high light use efficiency of B. incana under strong light conditions may help to explore mechanisms of plants' survival strategies. Therefore, the photosynthetic characteristics of B. incana grown under three different light intensities (field conditions (field): 200-1500μmolphotonsm(-2)s(-1); greenhouse high light (HL) conditons: 600μmolphotonsm(-2)s(-1); and greenhouse low light (LL) conditions: 100μmolphotonsm(-2)s(-1)) were investigated and compared with those of the model plant Arabidopsis thaliana (A. thaliana). Our results revealed that B. incana behaved differently in adjusting its photosynthetic activities under both HL and LL conditions compared with what A. thaliana did under the same conditions, suggesting that the potential of photosynthetic capacity of B. incana might be enhanced under strong light conditions. Under LL conditions, B. incana reached its maximum photosynthetic activity at a much higher light intensity than A. thaliana did, although their maximum photochemical efficiency of photosystem II (PSII) (F(v)/F(m)) was almost the same. When grown under HL conditions, B. incana showed much higher photosynthetic capacity than A. thaliana. A detailed analysis of the OJIP transient kinetics of B. incana under HL and LL conditions revealed that HL-grown B. incana possessed not only a high ability in regulating photosystem stoichiometry that ensured high linear electron transport, but also an enhanced availability of oxidized plastoquinone (PQ) pool which reduced non-photochemical quenching (NPQ), especially its slow components qT and qI, and increased the photochemical efficiency, which in turn, increased the electron transport. We suggest that the high ability in regulating photosystem stoichiometry and the high level of the availability of oxidized PQ pool in B. incana under strong light conditions play important roles in its ability to retain higher photosynthetic capacity under extreme environmental conditions. 相似文献