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101.
脓毒症是近年来的医学难题之一,迫切需要探讨新的治疗手段.以往研究发现,骨髓间充质干细胞具有免疫调节作用,免疫细胞因子白介素10(IL-10)是细胞因子分泌的抑制因子,具有很好的抗炎作用.因此构建了携带小鼠IL-10(mIL-10)的腺病毒载体,用它来感染骨髓间充质干细胞(BMSC),并通过载体上的绿色荧光蛋白来筛选过表达mIL-10基因的骨髓间充质干细胞(BMSC-mIL-10).随后,运用盲肠结扎穿孔法在小鼠体内建立脓毒症模型,并观察BMSC-mIL-10在脓毒症中的治疗作用.研究发现,和单纯BMSC治疗组相比,BMSC-mIL-10可以明显降低脓毒症老鼠体内炎症因子的产生,这包括TNF-α、IL-6、IL-1α和 IL-1β等,同时,BMSC-mIL-10治疗组小鼠的肺部和肾脏炎症反应减轻,体重丢失下降,死亡率明显降低.为进一步探讨BMSC-mIL-10治疗机制,运用Western blot和免疫荧光染色方法发现BMSC-mIL-10组上清液可以抑制巨噬细胞和中性粒细胞中LPS引起的NF-κB的激活.上述结果表明,骨髓间充质干细胞过表达IL-10有望成为脓毒症治疗的潜在手段之一. 相似文献
102.
为观察败血症时心肌肌浆网(SR)和核被膜(NE)的ryanodine受体的变化,采用结扎及穿刺盲肠(CLP)制作败血症动物模型,用密度梯度离心分离SR和NE,用放射配体结合法研究ryanodine受体的特征。结果表明,大鼠早期败血症(CLP后9h)时,SR的ryanodine受体的最大结合(Bmax)增加23%,NE的ryanodine受体的Bmax则增加1倍,二者比值降低39%(P<001);在晚期败血症(CLP后18h)时,SRryanodine受体的Bmax降低了38%,NE的ryanodine受体的Bmax增加16倍,二者比值降低76%;SR和NEryanodine受体的离解常数无显著改变。败血症时,SRryanodine受体早期上调,晚期下调,而NEryanodine受体均上调,这些变化可能与休克时相有关。 相似文献
103.
Giuseppe Mancuso Vitaliano Cusumano James A. Cook Edward Smith Francesco Squadrito Giovanna Blandino Giuseppe Teti 《FEMS immunology and medical microbiology》1994,9(1):49-54
Abstract The potential role of tumor necrosis factor α (TNFα) and eicosanoids in the pathogenesis of experimental neonatal sepsis models was investigated. Lethality was induced in neonatal rats by administration of heat killed group B streptococci (GBS, 7 mg kg−1 intracardially) or Salmonella enteritidis endotoxin (0.35 mg kg−1 intracardially). The relative efficacy of six compounds with putative TNFα and eicosanoid inhibitory actions were tested. These were: ibuprofen (3 and 20 mg kg−1 ), a cyclo-oxygenase inhibitor; CGS85515 (30 mg kg−1 ), a lipoxygenase inhibitor; LY203647 (30 mg kg−1 ), a leukotriene D4 receptor antagonist; pentoxifylline (10, 50 and 100 mg kg−1 ), a TNF inhibitor; cloricromene (2 and 10 mg kg−1 ), a thromboxane A2 synthetase inhibitor with TNFα inhibitory actions; and SKF86002 (2.5, 5, 10 and 20 mg kg−1 ), a dual cyclo-oxygenase/lipoxygenase inhibitor with TNFα inhibitory activity. Pentoxifylline, cloricromene and SKF86002, when given intraperitoneally 2 h before challenge, produced 45, 52 and 61% reductions, respectively, in plasma levels of TNFα at 2.5 h post-injection with killed GBS ( P < 0.05). On the contrary, pretreatment with ibuprofen, CGS85515 or LY203647 did not significantly affect TNFα levels. All compounds significantly attenuated the lethality by killed GBS and S. enteritidis endotoxin. These data suggest that TNFα and eicoisanoids contribute to the pathogenesis of shock induced by killed GBS and endotoxemia. 相似文献
104.
Hemoglobin released into the bloodstream is tightly bound by haptoglobin. The resulting complex (HpHb) is promptly cleared from the circulation and accumulates in the liver. A binding protein with a high affinity for HpHb has been solubilized from an acetone powder of rat liver and freed from an endogenous inhibitor by passage over a column of immobilized hemoglobin. An assay procedure has been developed whereby the bound HpHb is selectively precipitated by polyethylene glycol 6000. Employing this assay, the binding reaction was shown to be linear and saturable with respect to the ligand. In contrast to several previously described receptors for glycoproteins, the carbohydrate moiety of haptoglobin did not appear to participate in the binding of HpHb by the soluble receptor. 相似文献
105.
In an accelerated longitudinal design (ALD), individuals enter the study at different points of their growth trajectory and are observed over a short time span relative to the entire time span of interest. ALD data are combined across independent units to provide an estimate of an overall population curve and predictions of individual patterns of change. As a modest extension of the work of Ruppert et al. (2003, Semiparametric Regression, Cambridge University Press), we develop a computationally efficient procedure for the application of longitudinal semiparametric methods under ALD sampling schemes. We compare balanced and complete longitudinal designs to ALDs using the Berkeley Growth Study data and apply our method to longitudinal magnetic resonance imaging (MRI) brain structure size (volume) measurements from an ongoing developmental study. Potential applications extend beyond growth studies to many other fields in which cost and feasibility constraints impose restrictions on sample size and on the numbers and timings of repeated measurements across subjects. 相似文献
106.
As indicated by its name, tumor necrosis factor (TNF), cloned in 1985, was originally described as a macrophage-derived endogenous
mediator that can induce hemorrhagic necrosis of solid tumors and kill some tumor cell lines in vitro. Unfortunately, its
promising use as an anticancer agent was biased by its toxicity, which was clear soon from the first clinical trials with
TNF in cancer. Almost at the same time TNF was being developed as an anticancer drug, it became clear that TNF was identical
to a mediator responsible for cachexia associated with sepsis, which was termed cachectin. This research led to the finding
that TNF is, in fact, the main lethal mediator of sepsis and to the publication of a huge number of articles showing that
TNF inhibits the toxic effects of bacterial endotoxins, which are now described as systemic inflammatory response. Although
the clinical trials with anti-TNF in sepsis have not been successful thus far, undoubtedly as a result of the complexity of
this clinical setting, these studies ultimately led to the identification of TNF as a key inflammatory mediator and to the
development of anti-TNF molecules (soluble receptors and antibodies) for important diseases including rheumatoid arthritis
and Crohn’s disease. On the other side, the mechanisms by which TNF and related molecules induce cell death have been studied
in depth, and their knowledge might, in the future, suggest means of improve the therapeutic index of TNF in cancer. 相似文献
107.
Decreased translation initiation adversely impacts protein synthesis and contributes to the myocardial dysfunction produced by sepsis. Therefore, the purpose of the present study was to identify sepsis-induced changes in signal transduction pathways known to regulate translation initiation in cardiac muscle and to determine whether the stimulatory effects of leucine can reverse the observed defects. To address this aim, sepsis was produced by cecal ligation and puncture (CLP) in anesthetized rats and the animals studied in the fasted condition 24 h later. Separate groups of septic and time-matched control rats also received an oral gavage of leucine. To identify potential mechanisms responsible for regulating cap-dependent mRNA translation in cardiac muscle, several eukaryotic initiation factors (eIFs) were examined. Under basal conditions, hearts from septic rats demonstrated a redistribution of the rate-limiting factor eIF4E due to increased binding of the translational repressor 4E-BP1 with eIF4E. However, this change was independent of an alteration in the phosphorylation state of 4E-BP1. The phosphorylation of mTOR, S6K1, the ribosomal protein (rp) S6, and eIF4G was not altered in hearts from septic rats under basal conditions. In control rats, leucine failed to alter eIF4E distribution but increased the phosphorylation of S6K1 and S6. In contrast, in hearts from septic rats leucine acutely reversed the alterations in eIF4E distribution. However, the ability of leucine to increase S6K1 and rpS6 phosphorylation in septic hearts was blunted. Sepsis increased the content of tumor necrosis factor (TNF)-alpha in heart and pre-treatment of rats with a TNF antagonist prevented the above-mentioned sepsis-induced changes. These data indicate that oral administration of leucine acutely reverses sepsis-induced alterations eIF4E distribution observed under basal conditions but the anabolic actions of this amino acid on S6K1 and rpS6 phosphorylation remain blunted, providing evidence for a leucine resistance. Finally, TNFalpha, either directly or indirectly, appears to mediate the sepsis-induced defects in myocardial translation initiation. 相似文献
108.
IB Masters MM Eastburn PW Francis R Wootton PV Zimmerman RS Ware AB Chang 《Respiratory research》2005,6(1):16
Background
Flexible video bronchoscopes, in particular the Olympus BF Type 3C160, are commonly used in pediatric respiratory medicine. There is no data on the magnification and distortion effects of these bronchoscopes yet important clinical decisions are made from the images. The aim of this study was to systematically describe the magnification and distortion of flexible bronchoscope images taken at various distances from the object.Methods
Using images of known objects and processing these by digital video and computer programs both magnification and distortion scales were derived.Results
Magnification changes as a linear function between 100 mm (×1) and 10 mm (×9.55) and then as an exponential function between 10 mm and 3 mm (×40) from the object. Magnification depends on the axis of orientation of the object to the optic axis or geometrical axis of the bronchoscope. Magnification also varies across the field of view with the central magnification being 39% greater than at the periphery of the field of view at 15 mm from the object. However, in the paediatric situation the diameter of the orifices is usually less than 10 mm and thus this limits the exposure to these peripheral limits of magnification reduction. Intraclass correlations for measurements and repeatability studies between instruments are very high, r = 0.96. Distortion occurs as both barrel and geometric types but both types are heterogeneous across the field of view. Distortion of geometric type ranges up to 30% at 3 mm from the object but may be as low as 5% depending on the position of the object in relation to the optic axis.Conclusion
We conclude that the optimal working distance range is between 40 and 10 mm from the object. However the clinician should be cognisant of both variations in magnification and distortion in clinical judgements. 相似文献109.
脓毒血症早晚期肝细胞核被膜NTPase活性及poly(A)+mRNA核浆转运的变化 总被引:1,自引:0,他引:1
李载权 《中国应用生理学杂志》2000,(2)
目的和方法 :在盲肠结扎穿孔脓毒血症大鼠模型上 ,研究早晚期脓毒血症肝细胞核被膜核苷三磷酸酶 (NT Pase)活性及 poly(A) mRNA核浆转运的变化。结果 :脓毒血症早期NTPase活性增加而晚期活性降低 ,即早期Vmax与对照组比增加 6 2 % (ATP ,P <0 .0 5 )和 18% (GTP ,P <0 .0 5 ) ;晚期Vmax下降 2 6 % (ATP ,P <0 .0 5 )和5 6 % (GTP ,P <0 .0 5 )。脓毒血症仅晚期NTPase底物亲和力降低 ,即晚期Km与对照组比分别升高 2 6 % (ATP ,P<0 .0 5 )和 37% (GTP ,P <0 .0 5 )。脓毒血症早期 poly(A) mRNA核浆转运速率增加而晚期降低 ,即早期组 10min转运速率较对照组增加 2 7% (ATP ,P <0 .0 5 )和 30 % (GTP ,P <0 .0 5 ) ;晚期组降低 2 1% (P <0 .0 1)和 35 % (P <0 .0 1)。结论 :脓毒血症肝细胞核膜NTPase活性呈早期升高、晚期下降的双相变化与肝细胞核被膜 poly(A) mR NA核浆转运速率的早、晚期变化相平行 ,同时与脓毒血症血糖浓度的早、晚期变化相关。本实验在一定程度上解释了脓毒血症早晚期代谢双相变化发生的分子机理 相似文献
110.
Background Microflora populations residing in oropharyngeal and gastrointestinal sites defend against pathogenic bacterial colonization. Perturbations in these microbial communities may allow opportunistic pathogenic bacteria to establish themselves and cause morbidity and mortality from sepsis particularly after stressful experimental procedures. This study determined the prevalent facultative bacteria in a resident population of Macaca mulatta prior to use in experimentally induced immunosuppressive radiation studies.
Methods Standard microbiological methods were used to assess prevalent facultative bacteria in the oropharynx and rectum of 24 male M. mulatta .
Results The majority of the bacteria isolated from the oropharyngeal and rectal sites were gram-positive cocci. Species of Staphylococcus and Streptococcus predominated in all samples. Few gram-negative bacteria were isolated.
Conclusions Bacteriological assessment is recommended to identify predominant bacterial species to be prepared to provide appropriate antimicrobial therapy in non-human primates that are expected to undergo stressful immunocompromising procedures. 相似文献
Methods Standard microbiological methods were used to assess prevalent facultative bacteria in the oropharynx and rectum of 24 male M. mulatta .
Results The majority of the bacteria isolated from the oropharyngeal and rectal sites were gram-positive cocci. Species of Staphylococcus and Streptococcus predominated in all samples. Few gram-negative bacteria were isolated.
Conclusions Bacteriological assessment is recommended to identify predominant bacterial species to be prepared to provide appropriate antimicrobial therapy in non-human primates that are expected to undergo stressful immunocompromising procedures. 相似文献