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排序方式: 共有215条查询结果,搜索用时 31 毫秒
41.
Wissner A Brawner Floyd MB Rabindran SK Nilakantan R Greenberger LM Shen R Wang YF Tsou HR 《Bioorganic & medicinal chemistry letters》2002,12(20):2893-2897
The syntheses and biological evaluations of 4-anilinoquinoline-3-carbonitrile analogues of the three clinical lead 4-anilinoquinazolines Iressa, Tarceva, and CI-1033 are described. The EGFR and HER-2 kinase inhibitory activities and the cell growth inhibition of the two series are compared with each other and with the clinical lead EKB-569. Similar activities are observed between these two series. 相似文献
42.
Priyanka Sharma Gaurav Garg Arun Kumar Farhan Mohammad Sudha Ramesh Kumar Vinay Singh Tanwar Satish Sati Abhay Sharma Ganesan Karthikeyan Vani Brahmachari Shantanu Sengupta 《Gene》2014
Background
The alteration in the epigenome forms an interface between the genotype and the environment. Epigenetic alteration is expected to make a significant contribution to the development of cardiovascular disease where environmental interactions play a key role in disease progression. We had previously shown that global DNA hypermethylation per se is associated with coronary artery disease (CAD) and is further accentuated by high levels of homocysteine, a thiol amino acid which is an independent risk factor for cardiovascular disease and is also a key modulator of macromolecular methylation.Results
We have identified 72 differentially methylated regions (DMRs) that were hypermethylated in CAD patients in the background of varying homocysteine levels. Following deep bisulfite sequencing of a few of the selected DMRs, we found significantly higher methylation in CAD cases. We get six CpG sites in three DMRs that included the intronic region of C1QL4 gene and upstream region of CCDC47 and TGFBR3 genes.Conclusion
To the best of our knowledge, this is the first study to identify hypermethylated regions across the genome in patients with coronary artery disease. Further validation in different populations is necessary for this information to be used for disease risk assessment and management. 相似文献43.
Adriana Farias Silva Erick Leite Bastos Marcelo Der Torossian Torres André Luis Costa‐da‐Silva Rafaella Sayuri Ioshino Margareth Lara Capurro Flávio Lopes Alves Antonio Miranda Renata de Freitas Fischer Vieira Vani Xavier Oliveira Jr. 《Journal of peptide science》2014,20(8):640-648
Angiotensin II (AII) as well as analog peptides shows antimalarial activity against Plasmodium gallinaceum and Plasmodium falciparum, but the exact mechanism of action is still unknown. This work presents the solid‐phase synthesis and characterization of eight peptides corresponding to the alanine scanning series of AII plus the amide‐capped derivative and the evaluation of the antiplasmodial activity of these peptides against mature P. gallinaceum sporozoites. The Ala screening data indicates that the replacement of either the Ile5 or the His6 residues causes minor effects on the in vitro antiplasmodial activity compared with AII, i.e. AII (88%), [Ala6]‐AII (79%), and [Ala5]‐AII (75%). Analogs [Ala3]‐AII, [Ala1]‐AII, and AII‐NH2 showed antiplasmodial activity around 65%, whereas the activity of the [Ala8]‐AII, [Ala7]‐AII, [Ala4]‐AII, and [Ala2]‐AII analogs is lower than 45%. Circular dichroism data suggest that AII and the most active analogs adopt a β‐fold conformation in different solutions. All AII analogs, except [Ala4]‐AII and [Ala8]‐AII, show contractile responses and interact with the AT1 receptor, [Ala5]‐AII and [Ala6]‐AII. In conclusion, this approach is helpful to understand the contribution of each amino acid residue to the bioactivity of AII, opening new perspectives toward the design of new sporozoiticidal compounds. Copyright © 2014 European Peptide Society and John Wiley & Sons, Ltd. 相似文献
44.
Vani Pande Nivedita Mitra Saket Rahul Bagde Ramanujam Srinivasan Pananghat Gayathri 《The Journal of cell biology》2022,221(5)
MreB, the bacterial ancestor of eukaryotic actin, is responsible for shape in most rod-shaped bacteria. Despite belonging to the actin family, the relevance of nucleotide-driven polymerization dynamics for MreB function is unclear. Here, we provide insights into the effect of nucleotide state on membrane binding of Spiroplasma citri MreB5 (ScMreB5). Filaments of ScMreB5WT and an ATPase-deficient mutant, ScMreB5E134A, assemble independently of the nucleotide state. However, capture of the filament dynamics revealed that efficient filament formation and organization through lateral interactions are affected in ScMreB5E134A. Hence, the catalytic glutamate functions as a switch, (a) by sensing the ATP-bound state for filament assembly and (b) by assisting hydrolysis, thereby potentially triggering disassembly, as observed in other actins. Glu134 mutation and the bound nucleotide exhibit an allosteric effect on membrane binding, as observed from the differential liposome binding. We suggest that the conserved ATP-dependent polymerization and disassembly upon ATP hydrolysis among actins has been repurposed in MreBs for modulating filament organization on the membrane. 相似文献
45.
Events can sometimes appear longer or shorter in duration than other events of equal length. For example, in a repeated presentation of auditory or visual stimuli, an unexpected object of equivalent duration appears to last longer. Illusions of duration distortion beg an important question of time representation: when durations dilate or contract, does time in general slow down or speed up during that moment? In other words, what entailments do duration distortions have with respect to other timing judgments? We here show that when a sound or visual flicker is presented in conjunction with an unexpected visual stimulus, neither the pitch of the sound nor the frequency of the flicker is affected by the apparent duration dilation. This demonstrates that subjective time in general is not slowed; instead, duration judgments can be manipulated with no concurrent impact on other temporal judgments. Like spatial vision, time perception appears to be underpinned by a collaboration of separate neural mechanisms that usually work in concert but are separable. We further show that the duration dilation of an unexpected stimulus is not enhanced by increasing its saliency, suggesting that the effect is more closely related to prediction violation than enhanced attention. Finally, duration distortions induced by violations of progressive number sequences implicate the involvement of high-level predictability, suggesting the involvement of areas higher than primary visual cortex. We suggest that duration distortions can be understood in terms of repetition suppression, in which neural responses to repeated stimuli are diminished. 相似文献
46.
Sanjeev Khosla Prameelarani Kantheti Vani Brahmachari H. Sharat Chandra 《Chromosoma》1996,104(5):386-392
In mealybugs, chromatin condensation is related to both genomic imprinting and sex determination. The paternal chromosomal complement is condensed and genetically inactive in sons but not in daughters. During a study of chromatin organization in Planococcus lilacinus, digestion with micrococcal nuclease showed that 3% to 5% of the male genome is resistant to the enzyme. This Nuclease Resistant Chromatin (NRC) apparently has a nucleosomal organization. Southern hybridization of genomic DNA suggests that NRC sequences are present in both sexes and occur throughout the genome. Cloned NRC DNA is A+T-rich with stretches of adenines similar to those present in mouse -satellite sequences. NRC DNA also contains sequence motifs that are typically associated with the nuclear matrix. Salt-fractionation experiments showed that NRC sequences are matrix associated. These observations are discussed in relation to the unusual cytological features of mealybug chromosomes, including the possible existence of multiple centres of inactivation. 相似文献
47.
Light-enhanced dark respiration in mesophyll protoplasts from leaves of pea 总被引:2,自引:2,他引:0
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The respiratory oxygen uptake by mesophyll protoplasts of pea (Pisum sativum cv Arkel) was stimulated up to threefold after 15 minutes of illumination at an intensity of 1250 microeinsteins per square meter per second in the presence of 5 millimolar bicarbonate at 30°C. The extent of light-enhanced dark respiration (LEDR) increased progressively with duration of preillumination. The LEDR exhibited two phases. The initial high rate of respiration decreased in about 10 minutes to a lower steady value similar to that before illumination. The promotion of LEDR by the presence of bicarbonate and inhibition by glyceraldehyde or 3-(3,4-dichlorophenyl)-1,1-dimethylurea suggested that LEDR was dependent on products of photosynthetic carbon assimilation/electron transport. Thus, the photosynthetic products exert a markedly quick influence on dark respiration in mesophyll protoplasts. 相似文献
48.
Vani Nilakantan Huanling Liang Jordan Mortensen Erin Taylor Christopher P. Johnson 《Molecular and cellular biochemistry》2010,335(1-2):211-222
The role of mitochondrial KATP (mitoKATP) channels in renal ischemia-reperfusion injury is controversial with studies showing both protective and deleterious effects. In this study, we compared the effects of the putative mitoKATP opener, diazoxide, and the mitoKATP blocker, 5-hydroxydecanoate (5-HD) on cytotoxicity and apoptosis in tubular epithelial cells derived from rat (NRK-52E) and pig (LLC-PK1) following in vitro ischemic injury. Following ATP depletion-recovery, there was a significant increase in cytotoxicity in both NRK cells and LLC-PK1 cells although NRK cells were more sensitive to the injury. Diazoxide treatment attenuated cytotoxicity in both cell types and 5-HD treatment-increased cytotoxicity in the sensitive NRK cells in a superoxide-dependant manner. The protective effect of diazoxide was also reversed in the presence of 5-HD in ATP-depleted NRK cells. The ATP depletion-mediated increase in superoxide was enhanced by both diazoxide and 5-HD with the effect being more pronounced in the cells undergoing 5-HD treatment. Further, ATP depletion-induced activation of caspase-3 was decreased by diazoxide in NRK cells. In order to determine the signaling pathways involved in apoptosis, we examined the activation of Erk and JNK in ATP-depleted NRK cells. Diazoxide-activated Erk in ATP-depleted cells, but did not have any effect on JNK activation. In contrast, 5-HD did not impact Erk levels but increased JNK activation even under controlled conditions. Further, the use of a JNK inhibitor with 5-HD reversed the deleterious effects of 5-HD. This study demonstrates that in cells that are sensitive to ATP depletion-recovery, mitoKATP channels protect against ATP depletion-mediated cytotoxicity and apoptosis through Erk- and JNK-dependant mechanisms. 相似文献
49.
The levels of de novo DNA methyltransferase were studied during the development of a mealybug, Planococcus lilacinus. No enzyme activity could be detected in extracts from second instar females. But the enzyme occurs at high levels in third instar females and is maintained at that level during fourth instar when gametogenesis, fertilization and chromosome imprinting occur. These results suggest a developmental stage-specific modulation of levels of DNA methyltransferase. Assays with synthetic polymers showed that the enzyme can methylate not only polymers containing GpG but also those containing CpA and CpI. 相似文献
50.
Isabel Cristina Chica Acevedo Pedro Ismael Silva Jr Fernanda Dias Silva Iris Araújo Flvio Lopes Alves Cyntia Silva Oliveira Vani Xavier Oliveira Jr 《Journal of peptide science》2019,25(12)
IsCT1‐NH2 is a cationic antimicrobial peptide isolated from the venom of the scorpion Opisthacanthus madagascariensis that has a tendency to form an α‐helical structure and shows potent antimicrobial activity and also inopportunely shows hemolytic effects. In this study, five IsCT1 (ILGKIWEGIKSLF)‐based analogs with amino acid modifications at positions 1, 3, 5, or 8 and one analog with three simultaneous substitutions at the 1, 5, and 8 positions were designed. The net charge of each analog was between +2 and +3. The peptides obtained were characterized by mass spectrometry and analyzed by circular dichroism for their structure in different media. Studies of antimicrobial activity, hemolytic activity, and stability against proteases were also carried out. Peptides with a substitution at position 3 or 5 ([L]3‐IsCT1‐NH2, [K]3‐IsCT1‐NH2, or [F]5‐IsCT1‐NH2) showed no significant change in an activity relative to IsCT1‐NH2. The addition of a proline residue at position 8 ([P]8‐IsCT1‐NH2) reduced the hemolytic activity as well as the antimicrobial activity (MIC ranging 3.13‐50 μmol L?1), and the addition of a tryptophan residue at position 1 ([W]1‐IsCT1‐NH2) increased the hemolytic activity (MHC = 1.56 μmol L?1) without an improvement in antimicrobial activity. The analog [A]1[F]5[K]8‐IsCT1‐NH2, which carries three simultaneous modifications, presented increasing or equivalent values in antimicrobial activity (MIC approximately 0.38 and 12.5 μmol L?1) with a reduction in hemolytic activity. In addition, this analog presented the best resistance against proteases. This kind of strategy can find functional hotspots in peptide molecules in an attempt to generate novel potent peptide antibiotics. 相似文献