全文获取类型
收费全文 | 261篇 |
免费 | 22篇 |
出版年
2023年 | 3篇 |
2022年 | 1篇 |
2021年 | 23篇 |
2020年 | 4篇 |
2019年 | 12篇 |
2018年 | 17篇 |
2017年 | 9篇 |
2016年 | 12篇 |
2015年 | 21篇 |
2014年 | 23篇 |
2013年 | 37篇 |
2012年 | 27篇 |
2011年 | 21篇 |
2010年 | 13篇 |
2009年 | 14篇 |
2008年 | 9篇 |
2007年 | 10篇 |
2006年 | 5篇 |
2005年 | 3篇 |
2004年 | 2篇 |
2003年 | 5篇 |
2002年 | 2篇 |
2001年 | 1篇 |
1998年 | 2篇 |
1997年 | 1篇 |
1991年 | 1篇 |
1987年 | 1篇 |
1982年 | 1篇 |
1977年 | 1篇 |
1974年 | 1篇 |
1971年 | 1篇 |
排序方式: 共有283条查询结果,搜索用时 46 毫秒
51.
Umme Salma Suprabuddha Kundu Md. Nasim Ali Nirmal Mandal 《Plant Cell, Tissue and Organ Culture》2018,134(3):409-421
The present research focused on enhancing the production of wedelolactone through cell suspension culture (CSC) in Eclipta alba (L.) Hassk. With an aim of attaining a sustainable CSC, various plant growth regulators, elicitors and agitation speed were examined. Nodal segments of in vitro propagated plantlets induced the maximum percentage (93.47?±?0.61%) of callus inoculated on Murashige and Skoog (MS) medium fortified with picloram (2 mg L?1). The growth kinetics of CSC exhibited a sigmoid pattern with a lag phase (0–6 days), a log phase (6–18 days), a stationary phase (18–24 days) and then death phase thereafter. The highest biomass accumulation in CSC with 7.09?±?0.06 g 50 mL?1 fresh weight, 1.52?±?0.02 g 50 mL?1 dry cell weight, 1.34?±?0.01?×?106 cell mL?1 total cell count and 57.00?±?0.58% packed cell volume was obtained in the liquid MS medium supplemented with 1.5 mg L?1 picloram plus 0.5 mg L?1 kinetin at 120 rpm. High performance thin layer chromatography confirmed that yeast extract (biotic elicitor) at 150 mg L?1 accumulated more CSC biomass with 1.22-fold increase in wedelolactone (288.97?±?1.94 µg g?1 dry weight) content in comparison to the non-elicited CSC (237.78?±?0.04 µg g?1 dry weight) after 120 h of incubation. Contrastingly, methyl jasmonate (abiotic elicitor) did not alter the biomass but increased the wedelolactone content (259.32?±?1.06 µg g?1 dry weight) to an extent of 1.09-fold at 100 µM. Complete plantlet regeneration from CSC was possible on MS medium containing N6-benzyladenine (0.75 mg L?1) and abscisic acid (0.5 mg L?1). Thus, the establishment of protocol for CSC constitutes the bases for future biotechnological improvement studies in this crop. 相似文献
52.
53.
Monika Hilker Jens Schwachtje Margarete Baier Salma Balazadeh Isabel Bäurle Sven Geiselhardt Dirk K. Hincha Reinhard Kunze Bernd Mueller‐Roeber Matthias C. Rillig Jens Rolff Tina Romeis Thomas Schmülling Anke Steppuhn Joost van Dongen Sarah J. Whitcomb Susanne Wurst Ellen Zuther Joachim Kopka 《Biological reviews of the Cambridge Philosophical Society》2016,91(4):1118-1133
Experience and memory of environmental stimuli that indicate future stress can prepare (prime) organismic stress responses even in species lacking a nervous system. The process through which such organisms prepare their phenotype for an improved response to future stress has been termed ‘priming’. However, other terms are also used for this phenomenon, especially when considering priming in different types of organisms and when referring to different stressors. Here we propose a conceptual framework for priming of stress responses in bacteria, fungi and plants which allows comparison of priming with other terms, e.g. adaptation, acclimation, induction, acquired resistance and cross protection. We address spatial and temporal aspects of priming and highlight current knowledge about the mechanisms necessary for information storage which range from epigenetic marks to the accumulation of (dormant) signalling molecules. Furthermore, we outline possible patterns of primed stress responses. Finally, we link the ability of organisms to become primed for stress responses (their ‘primability’) with evolutionary ecology aspects and discuss which properties of an organism and its environment may favour the evolution of priming of stress responses. 相似文献
54.
Dorota?MoniesEmail author Hindi?N.?Alhindi Mohamed?A.?Almuhaizea Mohamed?Abouelhoda Anas?M.?Alazami Ewa?Goljan Banan?Alyounes Dyala?Jaroudi Abdulelah?AlIssa Khalid?Alabdulrahman Shazia?Subhani Mohamed?El-Kalioby Tariq?Faquih Salma?M.?Wakil Nada?A.?Altassan Brian?F.?Meyer Saeed?Bohlega 《Human genomics》2016,10(1):32
Background
Fifty random genetically unstudied families (limb-girdle muscular dystrophy (LGMD)/myopathy) were screened with a gene panel incorporating 759 OMIM genes associated with neurological disorders. Average coverage of the CDS and 10 bp flanking regions of genes was 99 %. All families were referred to the Neurosciences Clinic of King Faisal Specialist Hospital and Research Centre, Saudi Arabia. Patients presented with muscle weakness affecting the pelvic and shoulder girdle. Muscle biopsy in all cases showed dystrophic or myopathic changes. Our main objective was to evaluate a neurological gene panel as a first-line diagnostic test for LGMD/myopathies.Results
Our panel identified the mutation in 76 % of families (38/50; 11 novel). Thirty-four families had mutations in LGMD-related genes with four others having variants not typically associated with LGMD. The majority of cases had recessive inheritance with homoallelic pathogenic variants (97.4 %, 37/38), as expected considering the high rate of consanguinity in the study population. In one case, we detected a heterozygous mutation in DNAJB responsible for LGMD-1E. Our cohort included seven different subtypes of LGMD2. Mutations of DYSF were the most commonly identified cause of disease followed by that in CAPN3 and FKRP. Non-LGMD myopathies were due to mutations in genes associated with congenital disorder of glycosylation (ALG2), rigid spine muscular dystrophy 1 (SEPN1), inclusion body myopathy2/Nonaka myopathy (GNE), and neuropathy (WNK1). Whole exome sequencing (WES) of patients who remained undiagnosed with the neurological panel did not improve our diagnostic yield.Conclusions
Our neurological panel achieved a high clinical sensitivity (76 %) and is an effective first-line laboratory test in patients with LGMD and other myopathies. This sensitive, cost-effective, and rapid assay significantly assists clinical practice especially in these phenotypically and genetically heterogeneous disorders. Moreover, the application of the American College of Medical Genetics (ACMG) and Association for Molecular Pathology (AMP) guidelines applied in the classification of variant pathogenecity provides a clear interpretation for physicians on the relevance of such findings.55.
Sharad Verma Sonam Grover Chetna Tyagi Sukriti Goyal Salma Jamal Aditi Singh Abhinav Grover 《PloS one》2016,11(2)
p53, a tumor suppressor protein, has been proven to regulate the cell cycle, apoptosis, and DNA repair to prevent malignant transformation. MDM2 regulates activity of p53 and inhibits its binding to DNA. In the present study, we elucidated the MDM2 inhibition potential of polyphenols (Apigenin, Fisetin, Galangin and Luteolin) by MD simulation and MM/PBSA free energy calculations. All polyphenols bind to hydrophobic groove of MDM2 and the binding was found to be stable throughout MD simulation. Luteolin showed the highest negative binding free energy value of -173.80 kJ/mol followed by Fisetin with value of -172.25 kJ/mol. It was found by free energy calculations, that hydrophobic interactions (vdW energy) have major contribution in binding free energy. 相似文献
56.
57.
Economic Botany - Crop genetic diversity is important, but may be lost due to intentional or non-intentional selection processes. Jackfruit (Artocarpus heterophyllus) is the national fruit of... 相似文献
58.
George A Panda S Kudmulwar D Chhatbar SP Nayak SC Krishnan HH 《The Journal of biological chemistry》2012,287(7):5042-5058
Initiation, a major rate-limiting step of host protein translation, is a critical target in many viral infections. Chronic hepatitis C virus (HCV) infection results in hepatocellular carcinoma. Translation initiation, up-regulated in many cancers, plays a critical role in tumorigenesis. mTOR is a major regulator of host protein translation. Even though activation of PI3K-AKT-mTOR by HCV non-structural protein 5A (NS5A) is known, not much is understood about the regulation of host translation initiation by this virus. Here for the first time we show that HCV up-regulates host cap-dependent translation machinery in Huh7.5 cells through simultaneous activation of mTORC1 and eukaryotic translation initiation factor 4E (eIF4E) by NS5A. NS5A, interestingly, overexpressed and subsequently hyperphosphorylated 4EBP1. NS5A phosphorylated eIF4E through the p38 MAPK-MNK pathway. Both HCV infection and NS5A expression augmented eIF4F complex assembly, an indicator of cap-dependent translation efficiency. Global translation, however, was not altered by HCV NS5A. 4EBP1 phosphorylation, but not that of S6K1, was uniquely resistant to rapamycin in NS5A-Huh7.5 cells, indicative of an alternate phosphorylation mechanism of 4EBP1. Resistance of Ser-473, but not Thr-308, phosphorylation of AKT to PI3K inhibitors suggested an activation of mTORC2 by NS5A. NS5A associated with eIF4F complex and polysomes, suggesting its active involvement in host translation. This is the first report that implicates an HCV protein in the up-regulation of host translation initiation apparatus through concomitant regulation of multiple pathways. Because both mTORC1 activation and eIF4E phosphorylation are involved in tumorigenesis, we propose that their simultaneous activation by NS5A might contribute significantly to the development of hepatocellular carcinoma. 相似文献
59.
Ashok Kumar Sharma Saurabh Bharti Jagriti Bhatia Saroj Nepal Salma Malik Ruma Ray Santosh Kumari Dharamvir Singh Arya 《The Journal of nutritional biochemistry》2012,23(11):1482-1489
Increased oxidative stress and inflammation in obesity are the central and causal components in the pathogenesis and progression of cardiometabolic syndrome (CMetS). The aim of the study was to determine the potential role of sesamol (a natural powerful antioxidant and anti-inflammatory phenol derivative of sesame oil) in chronic high-cholesterol/high-fat diet (HFD)–induced CMetS in rats and to explore the molecular mechanism driving this activity. Rats were fed with HFD (55% calorie from fat and 2% cholesterol) for 60 days to induce obesity, dyslipidemia, insulin resistance (IR), hepatic steatosis and hypertension. On the 30th day, rats with total cholesterol >150 mg/dl were considered hypercholesterolemic and administered sesamol 2, 4 and 8 mg/kg per day for the next 30 days. Sesamol treatment decreased IR, hyperinsulinemia, hyperglycemia, dyslipidemia, TNF-α, IL-6, leptin, resistin, highly sensitive C-reactive protein (hs-CRP), hepatic transaminases and alkaline phosphatase, along with normalization of adiponectin, nitric oxide and arterial pressures in a dose-dependent fashion. Increased TBARS, nitrotyrosine and decreased antioxidant enzyme activities were also amended in HFD rats. Similarly, sesamol normalized hepatic steatosis and ultrastructural pathological alteration in hepatocytes, although the effect was more pronounced at 8 mg/kg. Furthermore, hepatic PPARγ, PPARα and e-NOS protein expressions were increased, whereas LXRα, SERBP-1c, P-JNK and NF-κB expression were decreased by sesamol treatment. These results suggest that sesamol attenuates oxidative stress, inflammation, IR, hepatic steatosis and hypertension in HFD-fed rats via modulating PPARγ, NF-κB, P-JNK, PPARα, LXRα, SREBP-1c and e-NOS protein expressions, thereby preventing CMetS. Thus, the present study demonstrates the therapeutic potential of sesamol in alleviating CMetS. 相似文献
60.
Salma Taboubi Fran?oise Garrouste Fabrice Parat Gilbert Pommier Emilie Faure Sylvie Monferran Hervé Kovacic Maxime Lehmann 《Molecular biology of the cell》2010,21(6):946-955
Insulin-like growth factor-I (IGF-I) activation of phosphoinositol 3-kinase (PI3K) is an essential pathway for keratinocyte migration that is required for epidermis wound healing. We have previously reported that activation of Gα(q/11)-coupled-P2Y2 purinergic receptors by extracellular nucleotides delays keratinocyte wound closure. Here, we report that activation of P2Y2 receptors by extracellular UTP inhibits the IGF-I–induced p110α-PI3K activation. Using siRNA and pharmacological inhibitors, we demonstrate that the UTP antagonistic effects on PI3K pathway are mediated by Gα(q/11)—and not G(i/o)—independently of phospholipase Cβ. Purinergic signaling does not affect the formation of the IGF-I receptor/insulin receptor substrate-I/p85 complex, but blocks the activity of a membrane-targeted active p110α mutant, indicating that UTP acts downstream of PI3K membrane recruitment. UTP was also found to efficiently attenuate, within few minutes, the IGF-I–induced PI3K-controlled translocation of the actin-nucleating protein cortactin to the plasma membrane. This supports the UTP ability to alter later migratory events. Indeed, UTP inhibits keratinocyte spreading and migration promoted by either IGF-I or a membrane-targeted active p110α mutant, in a Gα(q/11)-dependent manner both. These findings provide new insight into the signaling cross-talk between receptor tyrosine kinase and Gα(q/11)-coupled receptors, which mediate opposite effects on p110α-PI3K activity and keratinocyte migration. 相似文献