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41.
The central function of heterotrimeric GTP-binding proteins (G proteins) is the transduction of extracellular signals, via membrane receptors, leading to the activation of intracellular effectors. In addition to being associated with the plasma membrane, the α subunits of some of these proteins have also been localized in intracellular compartments. The mRNA of the G-protein inhibitory α subunit 2 (Gαi2) encodes two proteins, Gαi2 and sGi2, by an alternative splicing mechanism. sGi2 differs from Gαi2 in the C-terminal region and localizes in the Golgi in contrast to the plasma membrane localization of Gαi2. In this paper we show that the sequence specific to sGi2 can direct the Golgi localization of other Gαi subunits, but not of the stimulatory subunit Gαs or of a secreted protein. This indicates that, in addition to the sGi2 C-terminus, sequences located elsewhere in the protein are required to determine the Golgi localization. Inside the sGi2 C-terminal region we have identified a 14-amino-acid proline-rich motif which specifies the Golgi localization. Finally, we show that the sGi2 subunit, once activated, leaves the Golgi to be localized in the endoplasmic reticulum. 相似文献
42.
Rosana Rosseto de Oliveira Emiliana Cristina Melo Larissa Pereira Falavina Thais Aidar de Freitas Mathias 《PloS one》2015,10(11)
Background
Preterm birth is a serious public health problem, as it is linked to high rates of neonatal and child morbidity and mortality, with Brazil listed among the countries with the ten highest numbers of premature births. Nonetheless, knowledge is scarce regarding prematurity and associated factors in mid-sized cities. The objective of this study was to analyze the trend of preterm births and associated factors in a municipality located in the state of Paraná, Brazil.Methods
This was an ecological time series study of births recorded into the Live Birth Information System for residents of Maringá, Paraná, Brazil, between 2000 and 2013. The polynomial regression model was used for trend analysis of preterm birth, characteristics of the mother, gestation and delivery, and newborn. The association with preterm birth was analyzed using odds ratio (OR).Results
A total of 61,634 live births were analyzed, of which 5,632 were preterm births. Prematurity increased from 7.9% in 2000 to 11.2% in 2013 –an average increase of 0.54% per year (r2 = 0.93)–with a growing share of moderate preterm births (32 to <37 weeks), which rose from 7.0% in 2000 to 9.7% in 2013. Between 2011 and 2013, multiple pregnancy (OR = 16.64; CI = 13.24–20.92), inadequate number of prenatal visits (OR = 2.81; CI = 2.51–3.15), Apgar score below 7 at 1 (OR = 4.07; CI = 3.55–4.67) and 5 minutes (OR = 10.88; CI = 7.71–15.36), low birth weight (OR = 38.75; CI = 33.72–44.55) and congenital malformations (OR = 3.18; CI = 2.14–4.74) were associated with preterm birth. A growing trend was observed for multiple pregnancies, with an average annual increase of 0.32% (r2 = 0.90), as well as for C-section birth (2.38% yearly increase). Of all newborn characteristics, Apgar score below 7 at 5 minutes (-0.19% per year) and low birth weight (-1.43%) decreased, whereas congenital malformations rose (0.20% per year).Conclusions
Efforts are required to prevent premature delivery, particularly during the moderate period, as well as greater care during the prenatal period towards expectant mothers bearing multiple pregnancies, birth defects, in addition to reducing C-section birth as it may be linked to preterm birth. 相似文献43.
Céline Lamacchia Gaby Palmer Emiliana Rodriguez Praxedis Martin Solenne Vigne Christian A Seemayer Dominique Talabot-Ayer Jennifer E Towne Cem Gabay 《Arthritis research & therapy》2013,15(2):R38
Introduction
Interleukin (IL)-36 refers to three related IL-1 family cytokines, IL-36α, IL-36β, and IL-36γ, that bind to the IL-36 receptor (IL-36R). IL-36 exerts proinflammatory effects in skin and lung and stimulates T cell responses. In the present study, we examined the expression and function of IL-36R and its ligands in experimental arthritis.Methods
Collagen-induced arthritis (CIA), antigen-induced arthritis (AIA), and K/BxN serum transfer-induced arthritis were induced according to standard protocols. Messenger RNA levels for IL-36R and its ligands in the joints of mice with CIA were determined by RT-qPCR. Mice with CIA were injected with a blocking monoclonal anti-IL-36R, a blocking anti-IL-1RI, or their isotype-matched control antibodies at the time of arthritis onset. Anti-IL-36R or control antibodies were also injected at the time of AIA induction. Finally, IL-36R-deficient mice were examined in AIA and serum transfer-induced arthritis. The development and severity of arthritis were assessed by clinical and histological scoring.Results
IL-36R, IL-36Ra and IL-36γ mRNA were detected in the joints of mice with CIA, but their levels did not correlate with arthritis severity. As opposed to anti-IL-1RI antibody treatment, the injection of an anti-IL-36R antibody was devoid of effect on the development and severity of CIA. The severity of joint inflammation and structural damage in AIA was also unaltered by anti-IL-36R antibody treatment. Finally, the severity of AIA and K/BxN serum transfer-induced arthritis was similar in IL-36R-deficient and wild-type mice.Conclusions
The development and severity of experimental arthritis are independent of IL-36R signaling. 相似文献44.
Tsin W. Yeo Daniel A. Lampah Indri Rooslamiati Retno Gitawati Emiliana Tjitra Enny Kenangalem Ric N. Price Stephen B. Duffull Nicholas M. Anstey 《PloS one》2013,8(7)
Background
Decreased nitric oxide (NO) and hypoargininemia are associated with severe falciparum malaria and may contribute to severe disease. Intravenous L-arginine increases endothelial NO in moderately-severe malaria (MSM) without adverse effects. The safety, efficacy and pharmacokinetics of L-arginine or other agents to improve NO bioavailability in severe malaria have not been assessed.Methods
In an open-label pilot study of L-arginine in adults with severe malaria (ARGISM-1 Study), patients were randomized to 12 g L-arginine hydrochloride or saline over 8 hours together with intravenous artesunate. Vital signs, selected biochemical measures (including blood lactate and L-arginine) and endothelial NO bioavailability (using reactive hyperemia peripheral arterial tonometry [RH-PAT]) were assessed serially. Pharmacokinetic analyses of L-arginine concentrations were performed using NONMEM.Results
Six patients received L-arginine and two saline infusions. There were no deaths in either group. There were no changes in mean systolic (SBP) and diastolic blood pressure (DBP) or other vital signs with L-arginine, although a transient but clinically unimportant mean maximal decrease in SBP of 14 mmHg was noted. No significant changes in mean potassium, glucose, bicarbonate, or pH were seen, with transient mean maximal increases in plasma potassium of 0.3 mmol/L, and mean maximal decreases in blood glucose of 0.8 mmol/L and bicarbonate of 2.3 mEq/L following L-arginine administration. There was no effect on lactate clearance or RH-PAT index. Pharmacokinetic modelling (n = 4) showed L-arginine concentrations 40% lower than predicted from models developed in MSM.Conclusion
In the first clinical trial of an adjunctive treatment aimed at increasing NO bioavailability in severe malaria, L-arginine infused at 12 g over 8 hours was safe, but did not improve lactate clearance or endothelial NO bioavailability. Future studies may require increased doses of L-arginine.Trial Registration
ClinicalTrials.gov NTC00616304 相似文献45.
Fulton S Thibault D Mendez JA Lahaie N Tirotta E Borrelli E Bouvier M Tempel BL Trudeau LE 《The Journal of biological chemistry》2011,286(11):9360-9372
Impairments in axonal dopamine release are associated with neurological disorders such as schizophrenia and attention deficit hyperactivity disorder and pathophysiological conditions promoting drug abuse and obesity. The D2 dopamine autoreceptor (D2-AR) exerts tight regulatory control of axonal dopamine (DA) release through a mechanism suggested to involve K(+) channels. To evaluate the contribution of Kv1 voltage-gated potassium channels of the Shaker gene family to the regulation of axonal DA release by the D2-AR, the present study employed expression analyses, real time measurements of striatal DA overflow, K(+) current measurements and immunoprecipitation assays. Kv1.1, -1.2, -1.3, and -1.6 mRNA and protein were detected in midbrain DA neurons purified by fluorescence-activated cell sorting and in primary DA neuron cultures. In addition, Kv1.1, -1.2, and -1.6 were localized to DA axonal processes in the dorsal striatum. By means of fast scan cyclic voltammetry in striatal slice preparations, we found that the inhibition of stimulation-evoked DA overflow by a D2 agonist was attenuated by Kv1.1, -1.2, and -1.6 toxin blockers. A particular role for the Kv1.2 subunit in the process whereby axonal D2-AR inhibits DA overflow was established with the use of a selective Kv1.2 blocker and Kv1.2 knock-out mice. Moreover, we demonstrate the ability of D2-AR activation to increase Kv1.2 currents in co-transfected cells and its reliance on Gβγ subunit signaling along with the physical coupling of D2-AR and Kv1.2-containing channels in striatal tissue. These findings underline the contribution of Kv1.2 in the regulation of nigrostriatal DA release by the D2-AR and thereby offer a novel mechanism by which DA release is regulated. 相似文献
46.
Muhammad Hussein Gasem Herman Kosasih Emiliana Tjitra Bachti Alisjahbana Muhammad Karyana Dewi Lokida Aaron Neal C. Jason Liang Abu Tholib Aman Mansyur Arif Pratiwi Sudarmono Suharto Tuti Parwati Merati Vivi Lisdawati Siswanto Sophia Siddiqui H. Clifford Lane INA-RESPOND 《PLoS neglected tropical diseases》2022,16(6)
47.
An Exosome‐Based Vaccine Platform Imparts Cytotoxic T Lymphocyte Immunity Against Viral Antigens 下载免费PDF全文
48.
49.
Sandra Regina Maruyama Luiza Antunes Castro-Jorge José Marcos Chaves Ribeiro Luiz Gustavo Gardinassi Gustavo Rocha Garcia Lucinda Giampietro Brand?o Aline Rezende Rodrigues Marcos Ituo Okada Emiliana Pereira Abr?o Beatriz Rossetti Ferreira Benedito Antonio Lopes da Fonseca Isabel Kinney Ferreira de Miranda-Santos 《Memórias do Instituto Oswaldo Cruz》2014,109(1):38-50
50.
Lari A Lorenzi D Nigrelli D Brocchi E Faccini S Poli A 《Journal of wildlife diseases》2006,42(2):319-324
Tissue and blood samples were collected from 152 wild boars (Sus scrofa) from the Maremma area (Grosseto district, Central Italy) between November 2002 and January 2003. The presence of pseudorabies virus (PRV) antibodies, antigen, and DNA were confirmed by an enzyme-linked immunosorbent assay (ELISA), immunohistochemistry, and polymerase chain reaction (PCR), respectively. Of 152 animals, 62 (41%) were positive for viral antigen in tonsillar tissue. Of the 80 serum samples that were suitable for testing, 41 (51%) were positive for PRV antibodies. Positive immunohistochemistry results were confirmed by PCR. A significantly higher prevalence of PRV antigen and seroprevalence was detected in older animals. No differences were detected between males and females or for animals coming from different areas sampled. Results confirm that PRV is endemic in this wild boar population with a high prevalence of infection. The results of immunohistochemistry investigations demonstrated that a large number of wild boars harbor PRV in tonsillar tissues and should be considered as an important reservoir of PRV. 相似文献