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51.
Chunfeng Zhao Michio Hongo Brice Ilharreborde Kristin D. Zhao Bradford L. Currier Kai-Nan An 《PloS one》2015,10(10)
Background
Short-segment pedicle screw instrumentation (SSPI) is used for unstable burst fractures to correct deformity and stabilize the spine for fusion. However, pedicle screw loosening, pullout, or breakage often occurs due to the large moment applied during spine motion, leading to poor outcomes. The purpose of this study was to test the ability of a newly designed device, the Trans-Endplate Pedicle Pillar System (TEPPS), to enhance SSPI rigidity and decrease the screw bending moment with a simple posterior approach.Methods
Six human cadaveric spines (T11-L3) were harvested. A burst fracture was created at L1, and the SSPI (Moss Miami System) was used for SSPI fixation. Strain gauge sensors were mounted on upper pedicle screws to measure screw load bearing. Segmental motion (T12-L2) was measured under pure moment of 7.5 Nm. The spine was tested sequentially under 4 conditions: intact; first SSPI alone (SSPI-1); SSPI+TEPPS; and second SSPI alone (SSPI-2).Results
SSPI+TEPPS increased fixation rigidity by 41% in flexion/extension, 28% in lateral bending, and 37% in axial rotation compared with SSPI-1 (P<0.001), and it performed even better compared to SSPI-2 (P<0.001 for all). Importantly, the bending moment on the pedicle screws for SSPI+TEPPS was significantly decreased 63% during spine flexion and 47% in lateral bending (p<0.001).Conclusion
TEPPS provided strong anterior support, enhanced SSPI fixation rigidity, and dramatically decreased the load on the pedicle screws. Its biomechanical benefits could potentially improve fusion rates and decrease SSPI instrumentation failure. 相似文献52.
Frederique M Moret Cornelis E Hack Kim MG van der Wurff-Jacobs Wilco de Jager Timothy RDJ Radstake Floris PJG Lafeber Joel AG van Roon 《Arthritis research & therapy》2013,15(5):R155
Introduction
Myeloid dendritic cells (mDCs) are potent T cell-activating antigen-presenting cells that have been suggested to play a crucial role in the regulation of immune responses in many disease states, including rheumatoid arthritis (RA). Despite this, studies that have reported on the capacity of naturally occurring circulating mDCs to regulate T cell activation in RA are still lacking. This study aimed to evaluate the phenotypic and functional properties of naturally occurring CD1c (BDCA-1)+ mDCs from synovial fluid (SF) compared to those from peripheral blood (PB) of RA patients.Methods
CD1c+ mDC numbers and expression of costimulatory molecules were assessed by fluorescence-activated cell sorting (FACS) analysis in SF and PB from RA patients. Ex vivo secretion of 45 inflammatory mediators by mDCs from SF and PB of RA patients was determined by multiplex immunoassay. The capacity of mDCs from SF to activate autologous CD4+ T cells was measured.Results
CD1c+ mDC numbers were significantly increased in SF versus PB of RA patients (mean 4.7% vs. 0.6%). mDCs from SF showed increased expression of antigen-presenting (human leukocyte antigen (HLA) class II, CD1c) and costimulatory molecules (CD80, CD86 and CD40). Numerous cytokines were equally abundantly produced by mDCs from both PB and SF (including IL-12, IL-23, IL-13, IL-21). SF mDCs secreted higher levels of interferon γ-inducible protein-10 (IP-10), monokine induced by interferon γ (MIG) and, thymus and activation-regulated chemokine (TARC), but lower macrophage-derived chemokine (MDC) levels compared to mDCs from PB. mDCs from SF displayed a strongly increased capacity to induce proliferation of CD4+ T cells associated with a strongly augmented IFNγ, IL-17, and IL-4 production.Conclusions
This study suggests that increased numbers of CD1c+ mDCs in SF are involved in the inflammatory cascade intra-articularly by the secretion of specific T cell-attracting chemokines and the activation of self-reactive T cells. 相似文献53.
E Taslidere N Vardi H Parlakpinar A Yıldız B Taslidere MG Karaaslan 《Biotechnic & histochemistry》2013,88(7):485-495
We evaluated the effects of melatonin on acetylsalicylic acid (ASA) induced gastroduodenal and jejunal mucosal injury. We used 40 postpubertal rats divided randomly into five groups of eight animals. The control group consisted of untreated animals. The Mel group was injected intraperitoneally (i.p.) with 5 mg/kg melatonin. The ASA group was injected i.p. with 200 mg/kg ASA. The ASA + Mel group was injected i.p. with 5 mg/kg melatonin 45 min after administering 200 mg/kg ASA i.p. The Mel + ASA group was injected i.p. with 5 mg/kg melatonin 45 min before administering 200 mg/kg ASA i.p. We found no statistically significant differences in mean histopathological scores in the ASA + Mel group compared to the ASA group. ASA caused shortened villi and loss of the apical villus in the duodenum. The histopathological score was increased and villus height was decreased in the ASA group compared to untreated controls. Treatment with melatonin attenuated the histological damage. In the ASA group, occasional areas showed erosion of villi in the jejunum; however, differences in mean histopathological score in ASA group compared to the other groups were not statistically significant. Malondialdehyde (MDA), glutathione (GSH) and superoxide dismutase (SOD) activities were measured in stomach, duodenal and jejunum tissue. We found increased MDA activity in both stomach and duodenal tissues in the ASA group compared to the control group (p < 0.05). We found no statistically significant changes in MDA levels in jejunal tissue in the ASA group compared to the control group. We found no change in SOD activity in either stomach or duodenal tissues in the ASA group compared to the control group. We observed decreased SOD activity in jejunal tissue in the ASA group compared to the control group (p < 0.05). We detected no change in GSH activity in stomach, duodenal or jejunal tissues in the ASA group compared to the control group. The stomach damage was less in melatonin treated groups, but the lesions were not completely eliminated. The jejunum in the ASA group retained a nearly normal appearance. We found that melatonin exhibited some healing effects on ASA induced duodenal mucosal injury. 相似文献
54.
Currier JM Svoboda M Matoušek T Dědina J Stýblo M 《Metallomics : integrated biometal science》2011,3(12):1347-1354
Chronic ingestion of water containing inorganic arsenic (iAs) has been linked to a variety of adverse health effects, including cancer, hypertension and diabetes. Current evidence suggests that the toxic methylated trivalent metabolites of iAs, methylarsonous acid (MAs(III)) and dimethylarsinous acid (DMAs(III)) play a key role in the etiology of these diseases. Both MAs(III) and DMAs(III) have been detected in urine of subjects exposed to iAs. However, the rapid oxidation of DMAs(III) and, to a lesser extent, MAs(III) in oxygen-rich environments leads to difficulties in the analysis of these metabolites in samples of urine collected in population studies. Results of our previous work indicate that MAs(III) and DMAs(III) are relatively stable in a reducing cellular environment and can be quantified in cells and tissues. In the present study, we used the oxidation state-specific hydride generation-cryotrapping-atomic absorption spectroscopy (HG-CT-AAS) to examine the presence and stability of these trivalent metabolites in the liver of mice and in UROtsa/F35 cells exposed to iAs. Tri- and pentavalent metabolites of iAs were analyzed directly (without chemical extraction or digestion). Liver homogenates prepared in cold deionized water and cell culture medium and lysates were stored at either 0 °C or -80 °C for up to 22 days. Both MAs(III) and DMAs(III) were stable in homogenates stored at -80 °C. In contrast, DMAs(III) in homogenates stored at 0 °C began to oxidize to its pentavalent counterpart after 1 day; MAs(III) remained stable for at least 3 weeks under these conditions. MAs(III) and DMAs(III) generated in UROtsa/F35 cultures were stable for 3 weeks when culture media and cell lysates were stored at -80 °C. These results suggest that samples of cells and tissues represent suitable material for the quantitative, oxidation state-specific analysis of As in laboratory and population studies examining the metabolism or toxic effects of this metalloid. 相似文献
55.
Harrison RA Cook DA Renjifo C Casewell NR Currier RB Wagstaff SC 《Journal of Proteomics》2011,74(9):1768-1780
Antivenom is an effective treatment of snakebite but, because of the complex interplay of fiscal, epidemiological, therapeutic efficacy and safety issues, the mortality of snakebite remains unacceptably high. Efficiently combating this high level of preventable death amongst the world's most disadvantaged communities requires the globally-coordinated action of multiple intervention programmes. This is the overall objective of the Global Snakebite Initiative. This paper describes the challenges facing the research community to develop snakebite treatments that are more efficacious, safe and affordable than current therapy. 相似文献
56.
Eller MA Slike BM Cox JH Lesho E Wang Z Currier JR Darden JM Polonis VR Vahey MT Peel S Robb ML Michael NL Marovich MA 《PloS one》2011,6(9):e24254
Background
We conducted a novel pilot study comparing different delivery routes of ALVAC-HIV (vCP205), a canarypox vaccine containing HIV gene inserts: env, gag and pol. We explored the concept that direct ex vivo targeting of human dendritic cells (DC) would enhance the immune response compared to either conventional intramuscular or intradermal injections of the vaccine alone.Methodology/Principal Findings
Healthy HIV-1 uninfected volunteers were administered ALVAC-HIV or placebo by intramuscular injection (IM), intradermal injection (ID) or subcutaneous injection (SQ) of autologous ex vivo transfected DC at months 0, 1, 3 and 6. All vaccine delivery routes were well tolerated. Binding antibodies were observed to both the ALVAC vector and HIV-1 gp160 proteins. Modest cellular responses were observed in 2/7 individuals in the DC arm and 1/8 in the IM arm as determined by IFN-γ ELISPOT. Proliferative responses were most frequent in the DC arm where 4/7 individuals had measurable responses to multiple HIV-1 antigens. Loading DC after maturation resulted in lower gene expression, but overall better responses to both HIV-1 and control antigens, and were associated with better IL-2, TNF-α and IFN-γ production.Conclusions/Significance
ALVAC-HIV delivered IM, ID or SQ with autologous ex vivo transfected DC proved to be safe. The DC arm was most immunogenic. Proliferative immune responses were readily detected with only modest cytotoxic CD8 T cell responses. Loading mature DC with the live viral vaccine induced stronger immune responses than loading immature DC, despite increased transgene expression with the latter approach. Volunteers who received the autologous vaccine loaded mature DC developed a broader and durable immune response compared to those vaccinated by conventional routes.Trial Registration
ClinicalTrials.gov NCT00013572相似文献57.
Eller MA Blom KG Gonzalez VD Eller LA Naluyima P Laeyendecker O Quinn TC Kiwanuka N Serwadda D Sewankambo NK Tasseneetrithep B Wawer MJ Gray RH Marovich MA Michael NL de Souza MS Wabwire-Mangen F Robb ML Currier JR Sandberg JK 《PloS one》2011,6(4):e18779
HIV-1 disease progression is associated with persistent immune activation. However, the nature of this association is incompletely understood. Here, we investigated immune activation in the CD4 T cell compartment of chronically HIV-1 infected individuals from Rakai, Uganda. Levels of CD4 T cell activation, assessed as co-expression of PD-1, CD38 and HLA-DR, correlated directly to viral load and inversely to CD4 count. Deeper characterization of these cells indicated an effector memory phenotype with relatively frequent expression of Ki67 despite their PD-1 expression, and levels of these cells were inversely associated with FoxP3+ regulatory T cells. We therefore use the term deregulated effector memory (DEM) cells to describe them. CD4 T cells with a DEM phenotype could be generated by antigen stimulation of recall responses in vitro. Responses against HIV-1 and CMV antigens were enriched among the DEM CD4 T cells in patients, and the diverse Vβ repertoire of DEM CD4 T cells suggested they include diverse antigen-specificities. Furthermore, the levels of DEM CD4 T cells correlated directly to soluble CD14 (sCD14) and IL-6, markers of innate immune activation, in plasma. The size of the activated DEM CD4 T cell subset was predictive of the rate of disease progression, whereas IL-6 was only weakly predictive and sCD14 was not predictive. Taken together, these results are consistent with a model where systemic innate immune activation and chronic antigen stimulation of adaptive T cell responses both play important roles in driving pathological CD4 T cell immune activation in HIV-1 disease. 相似文献
58.
Background
Visceral adiposity in the setting of HIV infection and antiretroviral therapy (ART) is not fully understood, and treatment options remain limited. Telmisartan, an angiotensin receptor blocker and partial PPAR-γ agonist, has been shown to decrease visceral fat and improve metabolic and inflammatory parameters in HIV-uninfected subjects.Methods
HIV-infected subjects with HIV-1 RNA <50 copies/mL on ART and (women/men) waist circumference >94/95 cm or waist: hip ratio >0.88/0.94 received open-label telmisartan 40 mg po daily for 24 weeks. Adipose tissue (AT) volumes were quantified by L4–L5 single slice computed tomography. Metabolic and inflammatory markers were obtained fasting. Thirty-five subjects provided 80% power to detect a 10% 24-week decrease in visceral AT (VAT, two-sided α = 0.05).Results
Thirty-five subjects enrolled and completed the protocol. At entry (median or %): age 49 years, 43% female, 77% non-white, 91% non-smokers, CD4+ T cell count 590 cells/mm3, BMI 31 kg/m2. AT responses were heterogeneous, with statistically significant losses of median (IQR) total (TAT, 2.9% (−9.8, 0.7), p = 0.03) and subcutaneous (SAT, −2.7% (−9.8, 1.1), p = 0.03) AT, but not VAT (−2.7% (−20.5, 14.2), p = 0.53). Significant decreases in waist circumference and waist:hip ratio occurred (both p<0.001) without BMI or weight changes. In an exploratory analysis, significant increases in TNF-α occurred among female subjects without changes in other inflammatory or metabolic markers. No related adverse events occurred.Conclusions
Telmisartan was well tolerated. Small losses of AT from all depots were observed after 24 weeks of telmisartan therapy. Further study is needed to determine whether HIV-infected patients can receive metabolic benefits from telmisartan.Trial Registration
ClinicalTrials.gov NCT01088295相似文献59.
Ricardo Guerra Peixe Marcela Santana Bastos Boechat Alba Lucinia Peixoto Rangel Rh?nia Fran?a Gomes Rosa Maria Luiza Petzl-Erler Lilian MG Bahia-Oliveira 《Memórias do Instituto Oswaldo Cruz》2014,109(1):99-107
The association of single nucleotide polymorphisms (SNPs) in the interferon (IFN)-γ
gene ( IFNG ) with different types of retinal scar lesions
presumably caused by toxoplasmosis were investigated in a cross-sectional
population-based genetic study. Ten SNPs were investigated and after Bonferroni
correction, only the associations between SNPs rs2069718 and
rs3181035 with retinal/retinochoroidal scar lesions type A (most
severe scar lesions) and C (least severe scar lesions), respectively, remained
significant. The associations of two different IFNG SNPs with two
different types of retinal lesions attributable to toxoplasmosis support the
hypothesis that different inflammatory mechanisms underlie the development of these
lesions. The in vitro analysis of IFN-γ secretion by peripheral blood mononuclear
cells stimulated with Toxoplasma gondii antigens was also
investigated. The association between SNP rs2069718 and type A scar
lesions revealed that differential IFN-γ levels are correlated with distinct
genotypes. However, no correlation was observed with IFN-γ secretion levels and the
SNP rs3181035 , which was significantly associated with type C scar
lesions. Our findings strongly suggest that immunogenetic studies of individuals with
congenital or postnatally acquired infection are needed to better understand the role
of IFN-γ and its polymorphisms in the pathogenesis of ocular toxoplasmosis. 相似文献
60.