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排序方式: 共有293条查询结果,搜索用时 31 毫秒
91.
Liang GH Adebiyi A Leo MD McNally EM Leffler CW Jaggar JH 《American journal of physiology. Heart and circulatory physiology》2011,300(6):H2088-H2095
Hydrogen sulfide (H(2)S) is a gaseous signaling molecule that appears to contribute to the regulation of vascular tone and blood pressure. Multiple potential mechanisms of vascular regulation by H(2)S exist. Here, we tested the hypothesis that piglet cerebral arteriole smooth muscle cells generate ATP-sensitive K(+) (K(ATP)) currents and that H(2)S induces vasodilation by activating K(ATP) currents. Gas chromatography/mass spectrometry data demonstrated that after placing Na(2)S, an H(2)S donor, in solution, it rapidly (1 min) converts to H(2)S. Patch-clamp electrophysiology indicated that pinacidil (a K(ATP) channel activator), Na(2)S, and NaHS (another H(2)S donor) activated K(+) currents at physiological steady-state voltage (-50 mV) in isolated cerebral arteriole smooth muscle cells. Glibenclamide, a selective K(ATP) channel inhibitor, fully reversed pinacidil-induced K(+) currents and partially reversed (~58%) H(2)S-induced K(+) currents. Western blot analysis indicated that piglet arterioles expressed inwardly rectifying K(+) 6.1 (K(ir)6.1) channel and sulfonylurea receptor 2B (SUR2B) K(ATP) channel subunits. Pinacidil dilated pressurized (40 mmHg) piglet arterioles, and glibenclamide fully reversed this effect. Na(2)S also induced reversible and repeatable vasodilation with an EC(50) of ~30 μM, and this effect was partially reversed (~55%) by glibenclamide. Vasoregulation by H(2)S was also studied in pressurized resistance-size cerebral arteries of mice with a genetic deletion in the gene encoding SUR2 (SUR2 null). Pinacidil- and H(2)S-induced vasodilations were smaller in arterioles of SUR2 null mice than in wild-type controls. These data indicate that smooth muscle cell K(ATP) currents control newborn cerebral arteriole contractility and that H(2)S dilates cerebral arterioles by activating smooth muscle cell K(ATP) channels containing SUR2 subunits. 相似文献
92.
Dendritic cell maturation results in pronounced changes in glycan expression affecting recognition by siglecs and galectins 总被引:2,自引:0,他引:2
Bax M García-Vallejo JJ Jang-Lee J North SJ Gilmartin TJ Hernández G Crocker PR Leffler H Head SR Haslam SM Dell A van Kooyk Y 《Journal of immunology (Baltimore, Md. : 1950)》2007,179(12):8216-8224
Dendritic cells (DC) are the most potent APC in the organism. Immature dendritic cells (iDC) reside in the tissue where they capture pathogens whereas mature dendritic cells (mDC) are able to activate T cells in the lymph node. This dramatic functional change is mediated by an important genetic reprogramming. Glycosylation is the most common form of posttranslational modification of proteins and has been implicated in multiple aspects of the immune response. To investigate the involvement of glycosylation in the changes that occur during DC maturation, we have studied the differences in the glycan profile of iDC and mDC as well as their glycosylation machinery. For information relating to glycan biosynthesis, gene expression profiles of human monocyte-derived iDC and mDC were compared using a gene microarray and quantitative real-time PCR. This gene expression profiling showed a profound maturation-induced up-regulation of the glycosyltransferases involved in the expression of LacNAc, core 1 and sialylated structures and a down-regulation of genes involved in the synthesis of core 2 O-glycans. Glycosylation changes during DC maturation were corroborated by mass spectrometric analysis of N- and O-glycans and by flow cytometry using plant lectins and glycan-specific Abs. Interestingly, the binding of the LacNAc-specific lectins galectin-3 and -8 increased during maturation and up-regulation of sialic acid expression by mDC correlated with an increased binding of siglec-1, -2, and -7. 相似文献
93.
Lena Novack Slava Kogan Larisa Gimpelevich Michael Howell Abraham Borer Ciarán P. Kelly Daniel A. Leffler Victor Novack 《PloS one》2014,9(10)
Objective
An adverse effect of acid-suppression medications on the occurrence of Clostridium difficile infection (CDI) has been a common finding of many, but not all studies. We hypothesized that association between acid-suppression medications and CDI is due to the residual confounding in comparison between patients with infection to those without, predominantly from non-tested and less sick subjects. We aimed to evaluate the effect of acid suppression therapy on incidence of CDI by comparing patients with CDI to two control groups: not tested patients and patients suspected of having CDI, but with a negative test.Methods
We conducted a case-control study of adult patients hospitalized in internal medicine department of tertiary teaching hospital between 2005–2010 for at least three days. Controls from each of two groups (negative for CDI and non-tested) were individually matched (1∶1) to cases by primary diagnosis, Charlson comorbidity index, year of hospitalization and gender. Primary outcomes were diagnoses of International Classification of Diseases (ICD-9)–coded CDI occurring 72 hours or more after admission.Results
Patients with CDI were similar to controls with a negative test, while controls without CDI testing had lower clinical severity. In multivariable analysis, treatment by acid suppression medications was associated with CDI compared to those who were not tested (OR = 1.88, p-value = 0.032). Conversely, use of acid suppression medications in those who tested negative for the infection was not associated with CDI risk as compared to the cases (OR = 0.66; p = 0.059).Conclusions
These findings suggest that the reported epidemiologic associations between use of acid suppression medications and CDI risk may be spurious. The control group choice has an important impact on the results. Clinical differences between the patients with CDI and those not tested and not suspected of having the infection may explain the different conclusions regarding the acid suppression effect on CDI risk. 相似文献94.
Parfenova H Tcheranova D Basuroy S Fedinec AL Liu J Leffler CW 《American journal of physiology. Heart and circulatory physiology》2012,302(11):H2257-H2266
In newborn pigs, vasodilation of pial arterioles in response to glutamate is mediated via carbon monoxide (CO), a gaseous messenger endogenously produced from heme degradation by a heme oxygenase (HO)-catalyzed reaction. We addressed the hypothesis that ionotropic glutamate receptors (iGluRs), including N-methyl-D-aspartic acid (NMDA)- and 2-amino-3-(5-methyl-3-oxo-1,2-oxazol-4-yl) propanoic acid (AMPA)/kainate-type receptors, expressed in cortical astrocytes mediate glutamate-induced astrocyte HO activation that leads to cerebral vasodilation. Acute vasoactive effects of topical iGluR agonists were determined by intravital microscopy using closed cranial windows in anesthetized newborn pigs. iGluR agonists, including NMDA, (±)1-aminocyclopentane-cis-1,3-dicarboxylic acid (cis-ACPD), AMPA, and kainate, produced pial arteriolar dilation. Topical L-2-aminoadipic acid, a gliotoxin that selectively disrupts glia limitans, reduced vasodilation caused by iGluR agonists, but not by hypercapnia, bradykinin, or sodium nitroprusside. In freshly isolated and cultured cortical astrocytes constitutively expressing HO-2, iGluR agonists NMDA, cis-ACPD, AMPA, and kainate rapidly increased CO production two- to threefold. Astrocytes overexpressing inducible HO-1 had high baseline CO but were less sensitive to glutamate stimulation of CO production when compared with HO-2-expressing astrocytes. Glutamate-induced astrocyte HO-2-mediated CO production was inhibited by either the NMDA receptor antagonist (R)-3C4HPG or the AMPA/kainate receptor antagonist DNQX. Accordingly, either antagonist abolished pial arteriolar dilation in response to glutamate, NMDA, and AMPA, indicating functional interaction among various subtypes of astrocytic iGluRs in response to glutamate stimulation. Overall, these data indicate that the astrocyte component of the neurovascular unit is responsible for the vasodilation response of pial arterioles to topically applied glutamate via iGluRs that are functionally linked to activation of constitutive HO in newborn piglets. 相似文献
95.
Joyce JBC van Beers Annemiek Willemze Judith Stammen-Vogelzangs Jan W Drijfhout René EM Toes Ger J M Pruijn 《Arthritis research & therapy》2012,14(1):R35-16
Introduction
Fibronectin is one of the most abundant proteins present in the inflamed joint. Here, we characterized the citrullination of fibronectin in the joints of rheumatoid arthritis (RA) patients and studied the prevalence, epitope specificity and human leukocyte antigen (HLA) association of autoantibodies against citrullinated fibronectin in RA.Methods
Citrullinated residues in fibronectin isolated from RA patient synovial fluid were identified by mass spectrometry. The corresponding citrullinated and non-citrullinated peptides were synthesized and used to analyze the presence of autoantibodies to these peptides in RA sera and sera from other diseases and healthy controls by ELISA. The data were compared with risk factors like shared epitope HLA alleles and smoking, and with clinical features.Results
Five citrullinated residues were identified in fibronectin from RA synovial fluid. RA sera reacted in a citrulline-dependent manner with two out of four citrullinated fibronectin peptides, one of which contains two adjacent citrulline residues, in contrast to non-RA sera, which were not reactive. The most frequently recognized peptide (FN-Cit1035,1036, LTVGLTXXGQPRQY, in which × represents citrulline) was primarily targeted by anti-CCP (cyclic citrullinated peptide) 2-positive RA patients. Anti-FN-Cit1035,1036 autoantibodies were detected in 50% of established anti-CCP2-positive RA patients and in 45% of such patients from a early arthritis clinic. These antibodies appeared to be predominantly of the immunoglobulin G (IgG) isotype and to be associated with HLA shared epitope alleles (odds ratio = 2.11).Conclusions
Fibronectin in the inflamed synovia of RA patients can be citrullinated at least at five positions. Together with the flanking amino acids, three of these citrullinated residues comprise two epitopes recognized by RA autoantibodies. Anti-citrullinated fibronectin peptide antibodies are associated with HLA shared epitope alleles. 相似文献96.
A Bierhaus T Fleming S Stoyanov A Leffler A Babes C Neacsu SK Sauer M Eberhardt M Schnölzer F Lasischka WL Neuhuber TI Kichko I Konrade R Elvert W Mier V Pirags IK Lukic M Morcos T Dehmer N Rabbani PJ Thornalley D Edelstein C Nau J Forbes PM Humpert M Schwaninger D Ziegler DM Stern ME Cooper U Haberkorn M Brownlee PW Reeh PP Nawroth 《Nature medicine》2012,18(9):1445
97.
Galectin-1, -2, and -3 exhibit differential recognition of sialylated glycans and blood group antigens 总被引:5,自引:0,他引:5
Sean R Stowell Connie M Arthur Padmaja Mehta Kristen A Slanina Ola Blixt Hakon Leffler David F Smith Richard D Cummings 《The Journal of biological chemistry》2008,283(15):10109-10123
Human galectins have functionally divergent roles, although most of the members of the galectin family bind weakly to the simple disaccharide lactose (Galbeta1-4Glc). To assess the specificity of galectin-glycan interactions in more detail, we explored the binding of several important galectins (Gal-1, Gal-2, and Gal-3) using a dose-response approach toward a glycan microarray containing hundreds of structurally diverse glycans, and we compared these results to binding determinants on cells. All three galectins exhibited differences in glycan binding characteristics. On both the microarray and on cells, Gal-2 and Gal-3 exhibited higher binding than Gal-1 to fucose-containing A and B blood group antigens. Gal-2 exhibited significantly reduced binding to all sialylated glycans, whereas Gal-1 bound alpha2-3- but not alpha2-6-sialylated glycans, and Gal-3 bound to some glycans terminating in either alpha2-3- or alpha2-6-sialic acid. The effects of sialylation on Gal-1, Gal-2, and Gal-3 binding to cells also reflected differences in cellular sensitivity to Gal-1-, Gal-2-, and Gal-3-induced phosphatidylserine exposure. Each galectin exhibited higher binding for glycans with poly-N-acetyllactosamine (poly(LacNAc)) sequences (Galbeta1-4GlcNAc)(n) when compared with N-acetyllactosamine (LacNAc) glycans (Galbeta1-4GlcNAc). However, only Gal-3 bound internal LacNAc within poly(LacNAc). These results demonstrate that each of these galectins mechanistically differ in their binding to glycans on the microarrays and that these differences are reflected in the determinants required for cell binding and signaling. The specific glycan recognition by each galectin underscores the basis for differences in their biological activities. 相似文献
98.
Distribution of ecosystem C and N within contrasting vegetation types in a semiarid rangeland in the Great Basin,USA 总被引:1,自引:0,他引:1
Toby D. Hooker John M. Stark Urszula Norton A. Joshua Leffler Michael Peek Ron Ryel 《Biogeochemistry》2008,90(3):291-308
Semiarid sagebrush ecosystems are being transformed by wildfire, rangeland improvement techniques, and exotic plant invasions,
but the effects on ecosystem C and N dynamics are poorly understood. We compared ecosystem C and N pools to 1 m depth among
historically grazed Wyoming big sagebrush, introduced perennial crested wheatgrass, and invasive annual cheatgrass communities,
to examine whether the quantity and quality of plant inputs to soil differs among vegetation types. Natural abundance δ15N isotope ratios were used to examine differences in ecosystem N balance. Sagebrush-dominated sites had greater C and N storage
in plant biomass compared to perennial or annual grass systems, but this was predominantly due to woody biomass accumulation.
Plant C and N inputs to soil were greatest for cheatgrass compared to sagebrush and crested wheatgrass systems, largely because
of slower root turnover in perennial plants. The organic matter quality of roots and leaf litter (as C:N ratios) was similar
among vegetation types, but lignin:N ratios were greater for sagebrush than grasses. While cheatgrass invasion has been predicted
to result in net C loss and ecosystem degradation, we observed that surface soil organic C and N pools were greater in cheatgrass
and crested wheatgrass than sagebrush-dominated sites. Greater biomass turnover in cheatgrass and crested wheatgrass versus
sagebrush stands may result in faster rates of soil C and N cycling, with redistribution of actively cycled N towards the
soil surface. Plant biomass and surface soil δ15N ratios were enriched in cheatgrass and crested wheatgrass relative to sagebrush-dominated sites. Source pools of plant available
N could become 15N enriched if faster soil N cycling rates lead to greater N trace gas losses. In the absence of wildfire, if cheatgrass invasion
does lead to degradation of ecosystem function, this may be due to faster nutrient cycling and greater nutrient losses, rather
than reduced organic matter inputs. 相似文献
99.
Background
There is a frequent need to obtain sets of functionally equivalent homologous proteins (FEPs) from different species. While it is usually the case that orthology implies functional equivalence, this is not always true; therefore datasets of orthologous proteins are not appropriate. The information relevant to extracting FEPs is contained in databanks such as UniProtKB/Swiss-Prot and a manual analysis of these data allow FEPs to be extracted on a one-off basis. However there has been no resource allowing the easy, automatic extraction of groups of FEPs – for example, all instances of protein C. 相似文献100.
Satou Y Mineta K Ogasawara M Sasakura Y Shoguchi E Ueno K Yamada L Matsumoto J Wasserscheid J Dewar K Wiley GB Macmil SL Roe BA Zeller RW Hastings KE Lemaire P Lindquist E Endo T Hotta K Inaba K 《Genome biology》2008,9(10):R152-11