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排序方式: 共有118条查询结果,搜索用时 109 毫秒
71.
Arash Boroumand Nasr Deepika Ponnala Someshwar Rao Sagurthi Ramesh Kumar Kattamuri Vijaya Kumar Marri Suresh Gudala Chandana Lakkaraju Srinivas Bandaru Anuraj Nayarisseri 《Bioinformation》2015,11(6):307-315
Mammalian target of rapamycin (mTOR) is a key regulator of cell growth, proliferation and angiogenesis. mTOR signaling is
frequently hyper activated in a broad spectrum of human cancers thereby making it a potential drug target. The current drugs
available have been successful in inhibiting the mTOR signaling, nevertheless, show low oral bioavailability and suboptimal
solubility. Considering the narrow therapeutic window of the available inhibitors, through computational approaches, the present
study pursues to identify a compound with optimal oral bioavailability and better solubility properties in addition ensuing high
affinity between FKBP12 and FRB domain of mTOR. Current mTOR inhibitors; Everolimus, Temsirolimus Deforolimus and
Echinomycin served as parent molecules for similarity search with a threshold of 95%. The query molecules and respective similar
molecules were docked at the binding cleft of FKBP12 protein. Aided by MolDock algorithm, high affinity compounds against
FKBP12 were retrieved. Patch Dock supervised protein-protein interactions were established between FRB domain of mTOR and
ligand (query and similar) bound and free states of FKBP12. All the similar compounds thus retrieved showed better solubility
properties and enabled better complex formation of mTOR and FKBP12. In particular Everolimus similar compound PubChem ID:
57284959 showed appreciable drugs like properties bestowed with better solubility higher oral bioavailability. In addition this
compound brought about enhanced interaction between FKBP12 and FRB domain of mTOR. In the study, we report Everolimus
similar compound PubChem ID: 57284959 to be potential inhibitor for mTOR pathway which can overcome the affinity and
solubility concerns of current mTOR drugs.
Abbreviations
mTOR - Mammalian Target of Rapamycin, FRB domain - FKBP12-rapamycin associated protein, FKBP12 - FK506-binding protein 12, OPLS - Optimized Potentials for Liquid Simulations, Akt - RAC-alpha serine/threonine-protein kinase, PI3K - phosphatidylinositide 3-kinases. 相似文献72.
Pulse examination by palpation of a peripheral artery against a bony prominence is the most commonly used and widely accepted method. However this is subjective and thus prone to errors. Although pulse waveform was recorded in the 19th century, it did not gain popularity because of inconvenience in using the recording instruments and the absence of a sound theory to explain the wave forms recorded. Sphygmomanometry for recording blood pressure gained popularity as it was easy to record and had a sound theoretical background. Sphygmomanometry provides two extreme values of blood pressure but does not give a true representation of the blood pressure changes occurring in the entire cardiac cycle. Recently there has been resurgence in the analysis of the graphical recording of the pulse wave. Photoplethysmography is becoming a widely accepted technique in assessing the volume pulse. The whole review is about historical background, non-invasive methods of pulse recording, relation of the digital volume pulse to the pressure pulse and the advantages of recording the pressure pulse. 相似文献
73.
74.
Singh B Xu Y McLaughlin T Singh V Martinez JA Krishnan A Zochodne DW 《Journal of neurochemistry》2012,121(2):263-276
Insulin offers trophic support through receptors expressed widely on peripheral neurons. In this work, we studied whether peripheral sensory neurons demonstrate resistance to its trophic properties, a property relevant during type 2 diabetes mellitus or following supraphysiological therapy. Insulin receptors were not only localized to neuronal membranes and cytoplasm but also had a unique, previously unrecognized localization to neuronal nuclei. We confirmed that nanomolar doses increased neurite outgrowth of adult sensory neurons, but in response to micromolar doses of insulin, even following a brief 2-h exposure, survival and outgrowth of neurites were blunted. Neurons exposed to picomolar insulin concentrations in their media for 5 days had resistance to the impact of later nanomolar doses of insulin. Using a stripe assay seeded with insulin, neurites were more likely to reject higher doses of insulin. Insulin down-regulated mRNAs of the insulin receptor β subunit and up-regulated levels of GSK-3β, both potential mechanisms of insulin resistance, while down-regulating the protein expression of pAkt and pGSK-3β. Overall, these studies identify neuronal nuclear targeting of insulin and evidence for insulin-induced resistance to its trophic properties. The findings have implications for the understanding of the actions of insulin in the treatment of diabetes and neurological disorders. 相似文献
75.
J Bhagat A Kaur M Sharma AK Saxena BS Chadha 《World journal of microbiology & biotechnology》2012,28(3):963-971
This study reports the isolation of 63 endophytic fungal isolates from two traditional medicinal plants, Ocimum sanctum and Sapindus detergens from different locations of Amritsar, India. The functional characterization of the fungi for their ability to produce anti
bacterial and anti cancer agent was carried out. Sixteen strains were characterized at molecular level by sequencing the amplified
ITSI-5.8-ITSII region of rDNA. The phylogenetic tree resolved the endophytic fungi into different clades. The fungal endophytes
belonging to order Pleosporales (Alternaria sp., Phoma sojicola and Exserohilum sp.) were functionally versatile as they produced diverse biomolecules including antibacterial agent active against Mycobacterium smegmatis, as well as cytotoxic activity against different human cancer cell lines of lung, ovary, breast, prostrate, neuroblastoma
and colon. 相似文献
76.
Mayank Bhagat Chitresh Bhushan Goutam Saha Shinsuke Shimjo Katsumi Watanabe Joydeep Bhattacharya 《PloS one》2009,4(9)
Background
Photosensitive epilepsy is a type of reflexive epilepsy triggered by various visual stimuli including colourful ones. Despite the ubiquitous presence of colorful displays, brain responses against different colour combinations are not properly studied.Methodology/Principal Findings
Here, we studied the photosensitivity of the human brain against three types of chromatic flickering stimuli by recording neuromagnetic brain responses (magnetoencephalogram, MEG) from nine adult controls, an unmedicated patient, a medicated patient, and two controls age-matched with patients. Dynamical complexities of MEG signals were investigated by a family of wavelet entropies. Wavelet entropy is a newly proposed measure to characterize large scale brain responses, which quantifies the degree of order/disorder associated with a multi-frequency signal response. In particular, we found that as compared to the unmedicated patient, controls showed significantly larger wavelet entropy values. We also found that Renyi entropy is the most powerful feature for the participant classification. Finally, we also demonstrated the effect of combinational chromatic sensitivity on the underlying order/disorder in MEG signals.Conclusions/Significance
Our results suggest that when perturbed by potentially epileptic-triggering stimulus, healthy human brain manages to maintain a non-deterministic, possibly nonlinear state, with high degree of disorder, but an epileptic brain represents a highly ordered state which making it prone to hyper-excitation. Further, certain colour combination was found to be more threatening than other combinations. 相似文献77.
Background
Yersinia enterocolitica, an important food- and water-borne enteric pathogen is represented by six biovars viz. 1A, 1B, 2, 3, 4 and 5. Despite the lack of recognized virulence determinants, some biovar 1A strains have been reported to produce disease symptoms resembling that produced by known pathogenic biovars (1B, 2-5). It is therefore imperative to identify determinants that might contribute to the pathogeniCity of Y. enterocolitica biovar 1A strains. Y. enterocolitica invariably produces urease and the role of this enzyme in the virulence of biovar 1B and biovar 4 strains has been reported recently. The objective of this work was to study genetic organization of the urease (ure) gene complex of Y. enterocolitica biovar 1A, biochemical characterization of the urease, and the survival of these strains under acidic conditions in vitro. 相似文献78.
Bhagat L Zhu FG Yu D Tang J Wang H Kandimalla ER Zhang R Agrawal S 《Biochemical and biophysical research communications》2003,300(4):853-861
We demonstrate a new design for immunomodulatory CpG DNA containing two sequences each with as few as five or six-nucleotides joined together via 3(')-3(') linkers. These do not require the -PuPu(Py)CGPyPy- hexameric motif generally found essential for CpG DNA immune stimulation. These novel, short-immunomers show potent immunostimulatory activity manifested by IL-12 and IL-6 secretion in murine spleen cell and PBMC cultures and splenomegaly in vivo. Short-immunomers show strong activation of NF-kappaB and stress-activated signaling pathways and induce cytokines in J774 cell cultures. The same sequences also induce cytokines in healthy human PBMC cultures whereas conventional CpG DNA requires different optimal sequences for murine and human immune cells. Additionally, short-immunomers inhibit IL-5 secretion and induce IFN-gamma secretion in conalbumin-sensitized mouse spleen cell cultures, suggesting reversal of established Th2 responses to Th1 type responses. Short-immunomer also inhibits growth of MCF-7 human tumor xenograft in nude mice. This is the first report of activity with such short DNA sequences and also of sequences lacking hexameric motifs proposed in earlier studies. 相似文献
79.
Song AM Bhagat L Singh VP Van Acker GG Steer ML Saluja AK 《American journal of physiology. Gastrointestinal and liver physiology》2002,283(5):G1166-G1174
Cyclooxygenase-2 (COX-2), a widely distributed enzyme, plays an important role in inflammation. We have studied the role of COX-2 in acute pancreatitis and pancreatitis-associated lung injury using both the pharmacological inhibition of COX-2 and genetic deletion of COX-2. Pancreatitis was induced in mice by 12 hourly injections of cerulein. The severity of pancreatitis was assessed by measuring serum amylase, pancreatic trypsin activity, intrapancreatic sequestration of neutrophils, and acinar cell necrosis. The severity of lung injury was evaluated by measuring lactate dehydrogenase levels in the bronchoalveolar lavage fluid and by quantitating neutrophil sequestration in the lung. In both the pharmacologically inhibited and genetically altered mice, the severity of pancreatitis and pancreatitis-associated lung injury was reduced compared with the noninhibited strains of COX-2-sufficient mice. This reduction in injury indicates that COX-2 plays an important proinflammatory role in pancreatitis and its associated lung injury. Our findings support the concept that COX-2 inhibitors may play a beneficial role in the prevention of acute pancreatitis or in the reduction of its severity. 相似文献
80.
Bhatia M Saluja AK Singh VP Frossard JL Lee HS Bhagat L Gerard C Steer ML 《American journal of physiology. Gastrointestinal and liver physiology》2001,280(5):G974-G978
Complement factor C5a acting via C5a receptors (C5aR) is recognized as an anaphylotoxin and chemoattractant that exerts proinflammatory effects in many pathological states. The effects of C5a and C5aR in acute pancreatitis and in pancreatitis-associated lung injury were evaluated using genetically altered mice that either lack C5aR or do not express C5. Pancreatitis was induced by administration of 12 hourly injections of cerulein (50 microg/kg ip). The severity of pancreatitis was determined by measuring serum amylase, neutrophil sequestration in the pancreas, and acinar cell necrosis. The severity of lung injury was evaluated by measuring neutrophil sequestration in the lung and pulmonary microvascular permeability. In both strains of genetically altered mice, the severity of pancreatitis and pancreatitis-associated lung injury was greater than that noted in the comparison wild-type strains of C5aR- and C5-sufficient animals. This exacerbation of injury in the absence of C5a function indicates that, in pancreatitis, C5a exerts an anti-inflammatory effect. Potentially, C5a and its receptor are capable of both promoting and reducing the extent of acute inflammation. 相似文献