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61.
Agatha Aboe Balla Musa Joof Sarjo Kebba Kanyi Abba Hydara Philip Downs Simon Bush Paul Courtright 《PLoS neglected tropical diseases》2022,16(3)
Trachoma is the leading infectious cause of blindness in the world and has been known to be a major public health problem in The Gambia for over 60 years. Nationwide blindness surveys, including trachoma, in 1986 and 1996 provided the foundation for a comprehensive plan to implement a trachoma elimination strategy. Impact and pre-validation surveillance surveys in 2011–13 demonstrated that active trachoma was below WHO threshold for elimination but trichiasis remained a public health problem. Trichiasis-only surveys in 2019 demonstrated that trichiasis was below WHO thresholds for elimination and in 2020 the Government of The Gambia completed and submitted its dossier for validation of elimination as a public health problem. Challenges that The Gambia faced on the pathway to elimination included effective use of data for decision making, poor trichiasis surgical outcomes, lack of access to antibiotic treatment for low prevalence districts, high attrition of ophthalmic nurses trained as trichiasis surgeons, unexpected active trachoma in madrassas, the misalignment of elimination of active trachoma and trichiasis, trichiasis in urban settings, and maintaining the quality of surgery post-elimination when trichiasis cases are rare. Elimination of trachoma does not end with the submission of an elimination dossier; The Gambia will need to sustain monitoring and support over the coming years. 相似文献
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Pharmacological induction of ferritin prevents osteoblastic transformation of smooth muscle cells 下载免费PDF全文
Gergely Becs Abolfazl Zarjou Anupam Agarwal Katalin Éva Kovács Ádám Becs Mónika Nyitrai Enikő Balogh Emese Bányai John W. Eaton Paolo Arosio Maura Poli Viktória Jeney József Balla György Balla 《Journal of cellular and molecular medicine》2016,20(2):217-230
Vascular calcification is a frequent complication of atherosclerosis, diabetes and chronic kidney disease. In the latter group of patients, calcification is commonly seen in tunica media where smooth muscle cells (SMC) undergo osteoblastic transformation. Risk factors such as elevated phosphorus levels and vitamin D3 analogues have been identified. In the light of earlier observations by our group and others, we sought to inhibit SMC calcification via induction of ferritin. Human aortic SMC were cultured using β‐glycerophosphate with activated vitamin D3, or inorganic phosphate with calcium, and induction of alkaline phosphatase (ALP) and osteocalcin as well as accumulation of calcium were used to monitor osteoblastic transformation. In addition, to examine the role of vitamin D3 analogues, plasma samples from patients on haemodialysis who had received calcitriol or paricalcitol were tested for their tendency to induce calcification of SMC. Addition of exogenous ferritin mitigates the transformation of SMC into osteoblast‐like cells. Importantly, pharmacological induction of heavy chain ferritin by 3H‐1,2‐Dithiole‐3‐thione was able to inhibit the SMC transition into osteoblast‐like cells and calcification of extracellular matrix. Plasma samples collected from patients after the administration of activated vitamin D3 caused significantly increased ALP activity in SMC compared to the samples drawn prior to activated vitamin D3 and here, again induction of ferritin diminished the osteoblastic transformation. Our data suggests that pharmacological induction of ferritin prevents osteoblastic transformation of SMC. Hence, utilization of such agents that will cause enhanced ferritin synthesis may have important clinical applications in prevention of vascular calcification. 相似文献
65.
Adriana Baumlova Dominika Chalupska Bartosz Róźycki Marko Jovic Eva Wisniewski Martin Klima Anna Dubankova Daniel P Kloer Radim Nencka Tamas Balla Evzen Boura 《EMBO reports》2014,15(10):1085-1092
Phosphoinositides are a class of phospholipids generated by the action of phosphoinositide kinases with key regulatory functions in eukaryotic cells. Here, we present the atomic structure of phosphatidylinositol 4‐kinase type IIα (PI4K IIα), in complex with ATP solved by X‐ray crystallography at 2.8 Å resolution. The structure revealed a non‐typical kinase fold that could be divided into N‐ and C‐lobes with the ATP binding groove located in between. Surprisingly, a second ATP was found in a lateral hydrophobic pocket of the C‐lobe. Molecular simulations and mutagenesis analysis revealed the membrane binding mode and the putative function of the hydrophobic pocket. Taken together, our results suggest a mechanism of PI4K IIα recruitment, regulation, and function at the membrane. 相似文献
66.
Polyphosphoinositides are lipid signaling molecules generated from phosphatidylinositol (PtdIns) with critical roles in vesicular trafficking and signaling. It is poorly understood where PtdIns is located within cells and how it moves around between membranes. Here we identify a hitherto-unrecognized highly mobile membrane compartment as the site of PtdIns synthesis and a likely source of PtdIns of all membranes. We show that the PtdIns-synthesizing enzyme PIS associates with a rapidly moving compartment of ER origin that makes ample contacts with other membranes. In contrast, CDP-diacylglycerol synthases that provide PIS with its substrate reside in the tubular ER. Expression of a PtdIns-specific bacterial PLC generates diacylglycerol also in rapidly moving cytoplasmic objects. We propose a model in which PtdIns is synthesized in a highly mobile lipid distribution platform and is delivered to?other membranes during multiple contacts by yet-to-be-defined lipid transfer mechanisms. 相似文献
67.
Local and Regional Applications of Hydrogen Peroxide in the Control of Clostridial Myositis in Rabbits 下载免费PDF全文
J. W. Finney S. Haberman G. J. Race G. A. Balla J. T. Mallams 《Journal of bacteriology》1967,93(4):1430-1437
The intra-arterial infusion of hydrogen peroxide has been used as a method for producing a hyperoxic environment in experimental animals for the treatment of experimentally induced clostridial myositis. Eighty-five rabbits were employed in this study; 43 were controls and 42 were experimental animals. In the experimental study, 21 animals were treated with hydrogen peroxide by each route of administration. In this group, 52.4% of the animals receiving the intra-arterial infusion and 66.6% receiving intramuscular clysis survived. There were no survivors past 72 hr in the control group. 相似文献
68.
Fekete A Emri T Gyetvai A Gazdag Z Pesti M Varga Z Balla J Cserháti C Emody L Gergely L Pócsi I 《FEMS yeast research》2007,7(6):834-847
We tested the hypothesis that adaptation of Candida albicans to chronic oxidative stress inhibits the formation of hyphae and reduces pathogenicity. Candida albicans cells were exposed to increasing concentrations of t-butylhydroperoxide (tBOOH), a lipid peroxidation-accelerating agent, and mutants with heritable tBOOH tolerance were isolated. Hypha formation by the mutants was negligible on Spider agar, indicating that the development of oxidative stress tolerance prevented Candida cells from undergoing dimorphic switches. One of the mutants, C. albicans AF06, was five times less pathogenic in mice than its parental strain, due to its reduced germ tube-, pseudohypha- and hypha-forming capability, and decreased phospholipase secretion. An increased oxidative stress tolerance may therefore be disadvantageous when this pathogen leaves blood vessels and invades deep organs. The AF06 mutant was characterized by high intracellular concentrations of endogenous oxidants, reduced monounsaturated and polyunsaturated fatty acid contents, the continuous induction of the antioxidative defense system, decreased cytochrome c-dependent respiration, and increased alternative respiration. The mutation did not influence growth rate, cell size, cell surface, cellular ultrastructures, including mitochondria, or recognition by human polymorphonuclear leukocytes. The selection of oxidative stress-tolerant respiratory Candida mutants may also occur in vivo, when reduced respiration helps the fungus to cope with antimycotic agents. 相似文献
69.
Krenacs T Kiszner G Stelkovics E Balla P Teleki I Nemeth I Varga E Korom I Barbai T Plotar V Timar J Raso E 《Histochemistry and cell biology》2012,138(4):653-667
The 180?kDa transmembrane collagen XVII is known to anchor undifferentiated keratinocytes to the basement membrane in hemidesmosomes while constitutively shedding a 120?kDa ectodomain. Inherited mutations or auto-antibodies targeting collagen XVII cause blistering skin disease. Collagen XVII is down-regulated in mature keratinocytes but re-expressed in skin cancer. By recently detecting collagen XVII in melanocyte hyperplasia, here we tested its expression in benign and malignant melanocytic tumors using endodomain and ectodomain selective antibodies. We found the full-length collagen XVII protein in proliferating tissue melanocytes, basal keratinocytes and squamous cell carcinoma whereas resting melanocytes were negative. Furthermore, the cell-residual 60?kDa endodomain was exclusively detected in 62/79 primary and 15/18 metastatic melanomas, 8/9 melanoma cell lines, HT199 metastatic melanoma xenografts and atypical nests in 8/63 dysplastic nevi. The rest of 19 nevi including common, blue and Spitz subtypes were also negative. In line with the defective ectodomain, sequencing of COL17A1 gene revealed aberrations in the ectodomain coding region including point mutations. Collagen XVII immunoreaction-stained spindle cell melanomas, showed partly overlapping profiles with those of S100B, Melan A and HMB45. It was concentrated at vertical melanoma fronts and statistically associated with invasive phenotype. Antibody targeting the extracellular aa507-529 terminus of collagen XVII endodomain promoted apoptosis and cell adhesion, while inhibiting proliferation in HT199 cells. These results suggest that the accumulation of collagen XVII endodomain in melanocytic tumors is associated with malignant transformation to be a potential marker of malignancy and a target for antibody-induced melanoma apoptosis. 相似文献
70.
Phosphoinositides make up only a small fraction of membrane phospholipids yet they are of outmost significance in regulating membrane-associated signaling processes. A large number of inositol lipid kinases and phosphatases have evolved to control the rapid production and elimination of these lipids at specific cellular membrane compartments. For a long period of time, the only information about the spatial aspect of inositol lipid metabolism relied upon the immunostaining of enzymes or cell fractionation of the enzyme activities that acted upon these lipids. Recent advances in the understanding of the nature of protein-inositol lipid interactions permitted the design of fluorescent molecular probes that can interact with inositol lipids in a specific manner allowing imaging of phosphoinositide dynamics in live cells. This approach has rapidly gained high popularity, but also provoked criticisms and debate about its limitations. In this review, we will summarize our experience with using these molecular tools and address some issues that most often come up in discussions concerning the usefulness and drawbacks of this technique. The most important value of these debates is that they also challenge our preconceived views of how phosphoinositides regulate cellular functions. 相似文献