全文获取类型
收费全文 | 245篇 |
免费 | 14篇 |
出版年
2022年 | 3篇 |
2021年 | 5篇 |
2020年 | 2篇 |
2019年 | 1篇 |
2018年 | 1篇 |
2017年 | 5篇 |
2016年 | 5篇 |
2015年 | 20篇 |
2014年 | 11篇 |
2013年 | 11篇 |
2012年 | 27篇 |
2011年 | 18篇 |
2010年 | 13篇 |
2009年 | 10篇 |
2008年 | 15篇 |
2007年 | 14篇 |
2006年 | 11篇 |
2005年 | 13篇 |
2004年 | 22篇 |
2003年 | 9篇 |
2002年 | 16篇 |
1999年 | 3篇 |
1998年 | 2篇 |
1997年 | 5篇 |
1996年 | 3篇 |
1995年 | 2篇 |
1994年 | 1篇 |
1993年 | 1篇 |
1991年 | 1篇 |
1990年 | 1篇 |
1986年 | 1篇 |
1985年 | 1篇 |
1984年 | 1篇 |
1983年 | 1篇 |
1980年 | 1篇 |
1976年 | 1篇 |
1965年 | 1篇 |
1956年 | 1篇 |
排序方式: 共有259条查询结果,搜索用时 390 毫秒
131.
Lorenza Pugni Carlo Pietrasanta Silvano Milani Claudia Vener Andrea Ronchi Mariella Falbo Milena Arghittu Fabio Mosca 《PloS one》2015,10(12)
Objective
Presepsin (soluble CD14 subtype) has been shown to be beneficial as a sepsis marker in adults. Nevertheless, very few data are available in neonates. The aim of the present study was to determine reference ranges of presepsin in term and preterm neonates.Methods
Healthy term neonates and preterm neonates without clinical signs of infection admitted to the Neonatal Unit were consecutively enrolled. Presepsin concentrations in whole blood were measured using a point-of-care assay system located in the Unit. Demographic data, antenatal and perinatal variables commonly affecting C-reactive protein and procalcitonin values were considered.Results
Of the 684 neonates enrolled in the study, 484 (70.8%) were born at term and 200 (29.2%) were preterm (24–36 weeks’ gestation). In term infants, presepsin median value was 603.5 pg/mL (interquartile range: 466.5–791 pg/mL; 5th and 95th centiles: 315 and 1178 pg/mL respectively). In preterm infants, presepsin median value was slightly higher, equal to 620 pg/mL (interquartile range: 503–864 pg/mL; 5th and 95th centiles: 352 and 1370 pg/mL respectively). The reference ranges of presepsin we determined were much higher than those seen in healthy adults. No correlation between presepsin levels and postnatal age was observed, as well as no significant difference was demonstrated in preterm neonates at different gestational ages. None of the variables analyzed affected presepsin levels at a clinical significant extent.Conclusion
For the first time, this study provides reference ranges of presepsin in term and preterm neonates. Having reliable reference values is crucial for obtaining an adequate diagnostic accuracy. Based on our results, most variables commonly affecting C-reactive protein and procalcitonin values do not affect presepsin levels, which suggests that presepsin could be an effective sepsis marker. Further investigations in large groups of neonates with sepsis are needed to determine the diagnostic and prognostic value of this biomarker. 相似文献132.
Giuseppe Santarpia Salvatore De Rosa Alberto Polimeni Salvatore Giampà Mariella Micieli Antonio Curcio Ciro Indolfi 《PloS one》2015,10(5)
BackgroundUse of the non-vitamin K antagonist oral anticoagulants (NOACs) is endorsed by current guidelines for stroke prevention in patients with atrial fibrillation (AF). However efficacy and safety of NOACs in patients undergoing catheter ablation (RFCA) of AF has not been well established yet.ObjectivesTo perform a meta-analysis of all studies comparing NOACs and vitamin K antagonist oral anticoagulants (VKAs) in patients undergoing RFCA.ResultsThere was no significant difference in thromboembolic complications (RR 1.39; p=0.13). Bleeding complications were significantly lower in the NOACs-treated arm as compared to VKAs (RR=0.67, p<0.001). Interestingly, a larger number of thromboembolic events was found in the VKAs-treated arm in those studies where VKAs had been interrupted during the periprocedural phase (RR=0.68; p=ns). In this same subgroup a significantly higher incidence of both minor (RR=0.54; p=0.002) and major bleeding (RR=0.41; p=0.01) events was recorded. Conversely, the incidence of thromboembolic events in the VKAs-treated arm was significantly lower in those studies with uninterrupted periprocedural anticoagulation treatment (RR=1.89; p=0.02).LimitationsAs with every meta-analysis, no patients-level data were available.
Conclusions and Implications
The use of NOACs in patients undergoing RFCA is safe, given the lower incidence of bleedings observed with NOACs. On the other side, periprocedural interruption of VKAs and bridging with heparin is associated with a higher bleeding rate with no significant benefit on onset of thromboembolic events. 相似文献133.
Dissociation of bovine odorant binding protein (bOBP) dimers to monomers at pH 2.5 has been confirmed through size exclusion chromatography experiments. Moreover, structural and binding properties of the acidic monomer and neutral dimer have been compared using a combination of experimental (circular dichroism and fluorescence) and computational (molecular dynamics) techniques. The secondary and tertiary structures of bOBP are largely maintained at acidic pH, but molecular dynamics simulations suggest the loop regions (N-terminal residues, Omega-loop and C-terminal segments) are more relaxed and Phe36 and Tyr83 residues are involved in the regulation of the binding cavity entrance. The formation of a molten globule state at acidic pH, suggested by the strong enhancement of fluorescence of 8-anilino-1-naphtalenesulphonic acid (ANS), is not confirmed by any significant change in the near UV circular dichroism spectrum. Functionality measurements, deduced from the interaction of bOBP with 1-amino-anthracene (AMA), show that the binding capacity of the protein at acidic pH is preserved, though slightly looser than at neutral pH. Unfolding of acidic bOBP, induced by guanidinium chloride (GdnHCl), was investigated by means of CD spectroscopy, steady state fluorescence, fluorescence anisotropy and light scattering. The stability of the acidic monomer is lower than that of the neutral dimer, owing to the loss of the swapping interactions, but renaturation is completely reversible. Finally, in contrast with the neutral dimer, at low denaturant concentration some aggregation of the acidic monomer, which vanishes before the unfolding transition, has been observed. 相似文献
134.
Superina M Boily P 《Comparative biochemistry and physiology. Part A, Molecular & integrative physiology》2007,148(4):893-898
Hibernation and daily torpor are physiological strategies to cope with energetic challenges that occur in many mammalian and avian taxa, but no reliable information exists about daily torpor or hibernation for any xenarthran. Our objective was to determine whether the pichi (Zaedyus pichiy), a small armadillo (Xenarthra, Dasypodidae) that inhabits arid and semi-arid habitats in central and southern Argentina and Chile, enters shallow daily torpor or prolonged deep hibernation during winter when environmental temperature and food availability are low. We studied body temperature changes during winter in semi-captive pichis by means of temperature dataloggers implanted subcutaneously. All individuals entered hibernation, characterized by torpor events of 75 ± 20 h during which the subcutaneous temperature (Tsc) decreased to 14.6 ± 2.1 °C. These events were interrupted by periods of euthermia of 44 ± 38 h with a Tsc of 29.1 ± 0.7 °C. After the hibernation season, daily torpor bouts of 4 to 6 h occurred irregularly, with Tsc dropping to as low as 24.5 °C. We conclude that the pichi is a true hibernator and can enter daily torpor outside of the hibernation season. 相似文献
135.
The genetic basis of a craniofacial disease provides insight into COPII coat assembly 总被引:3,自引:0,他引:3
Fromme JC Ravazzola M Hamamoto S Al-Balwi M Eyaid W Boyadjiev SA Cosson P Schekman R Orci L 《Developmental cell》2007,13(5):623-634
Proteins trafficking through the secretory pathway must first exit the endoplasmic reticulum (ER) through membrane vesicles created and regulated by the COPII coat protein complex. Cranio-lenticulo-sutural dysplasia (CLSD) was recently shown to be caused by a missense mutation in SEC23A, a gene encoding one of two paralogous COPII coat proteins. We now elucidate the molecular mechanism underlying this disease. In vitro assays reveal that the mutant form of SEC23A poorly recruits the Sec13-Sec31 complex, inhibiting vesicle formation. Surprisingly, this effect is modulated by the Sar1 GTPase paralog used in the reaction, indicating distinct affinities of the two human Sar1 paralogs for the Sec13-Sec31 complex. Patient cells accumulate numerous tubular cargo-containing ER exit sites devoid of observable membrane coat, likely representing an intermediate step in COPII vesicle formation. Our results indicate that the Sar1-Sec23-Sec24 prebudding complex is sufficient to form cargo-containing tubules in vivo, whereas the Sec13-Sec31 complex is required for membrane fission. 相似文献
136.
Marianne Brugna M.T. Giudici-Orticoni Silvia Spinelli Kieron Brown Mariella Tegoni Mireille Bruschi 《Proteins》1998,33(4):590-600
Hydrogenases from Desulfovibrio are found to catalyze hydrogen uptake with low potential multiheme cytochromes, such as cytochrome c3, acting as acceptors. The production of Fe-only hydrogenase from Desulfovibrio vulgaris Hildenborough was improved with respect to the growth phase and media to determine the best large-scale bacteria growth conditions. The interaction and electron transfer from Fe-only hydrogenase to multiheme cytochrome has been studied in detail by both BIAcore and steady-state measurements. The electron transfer between [Fe] hydrogenase and cytochrome c3 appears to be a cooperative phenomenon (h = 1.37). This behavior could be related to the conductivity properties of multihemic cytochromes. An apparent dissociation constant was determined (2 × 10-7 M). The importance of the cooperativity for contrasting models proposed to describe the functional role of the hydrogenase/cytochrome c3 complex is discussed. Presently, the only determined structure is from [NiFe] hydrogenase and there are no obvious similarities between [NiFe] and [Fe] hydrogenase. Furthermore, no crystallographic data are available concerning [Fe] hydrogenase. The first results on crystallization and X-ray crystallography are reported. Proteins 33:590–600, 1998. © 1998 Wiley-Liss, Inc. 相似文献
137.
Sala R Jefferies WA Walker B Yang J Tiong J Law SK Carlevaro MF Di Marco E Vacca A Cancedda R Cancedda FD Ribatti D 《European journal of cell biology》2002,81(11):599-607
Melanotransferrin is a member of the transferrin family, which is comprised of serum transferrin, lactoferrin and ovotransferrin, and is highly expressed on melanoma cells compared to normal melanocytes. Since melanoma is an highly vascularized tumour that expresses melanotransferrin at high levels, we tested purified recombinant melanotransferrin for its capability to induce angiogenesis in the chick chorioallantoic membrane. Macroscopic and microscopic evaluation of the vascular density demonstrated that melanotransferrin exerts an angiogenic response quantitatively similar to that elicited by fibroblast growth factor-2. Overexpression of vascular endothelial growth factor-receptor-2 was observed in newly formed vessels, suggesting that the angiogenic activity of melanotransferrin may depend on activation of endogenous vascular endothelial growth factor. In addition, when antibodies against vascular endothelial growth factor were included in the assay, the angiogenic response was inhibited by 50%. In a Boyden chamber assay purified recombinant melanotransferrin induced chemotactic migration of vascular cells, which was decreased in the the presence of anti-vascular endothelial growth factor antibodies suggesting an involvement of vascular endothelial growth factor present in endothelial cells also in this assay. However, melanotransferrin was found not to directly bind to integrin alphavbeta3 or the vascular endothelial growth factor-receptor-2 as assessed in a BlAcore assay. A possible correlation between vascularization occurring during melanoma progression and the expression of melanotransferrin and vascular endothelial growth factor was established by immunolocalization of the two factors in sections of melanoma at different clinical steps of melanoma progression. These latter data strongly imply that melanotransferrin may participate in the vascularization of solid tumours and that inhibition of melanotransferrin could form the basis for intervention in tumours which use this pathway. 相似文献
138.
Mariella Fischer-Williams 《BMJ (Clinical research ed.)》1956,1(4966):533-538
139.
140.
Badreddine Douzi Eric Durand C��dric Bernard S��bastien Alphonse Christian Cambillau Alain Filloux Mariella Tegoni Rom�� Voulhoux 《The Journal of biological chemistry》2009,284(50):34580-34589
Gram-negative bacteria use the sophisticated type II secretion system (T2SS) to secrete a large number of exoproteins into the extracellular environment. Five proteins of the T2SS, the pseudopilins GspG-H-I-J-K, are proposed to assemble into a pseudopilus involved in the extrusion of the substrate through the outer membrane channel. Recent structural data have suggested that the three pseudopilins GspI-J-K are organized in a trimeric complex located at the tip of the GspG-containing pseudopilus. In the present work we combined two biochemical techniques to investigate the protein-protein interaction network between the five Pseudomonas aeruginosa Xcp pseudopilins. The soluble domains of XcpT-U-V-W-X (respectively homologous to GspG-H-I-J-K) were purified, and the interactions were tested by surface plasmon resonance and affinity co-purification in all possible combinations. We found an XcpVI-WJ-XK complex, which demonstrates that the crystallized trimeric complex also exists in the P. aeruginosa T2SS. Interestingly, our systematic approach revealed an additional and yet uncharacterized interaction between XcpUH and XcpWJ. This observation suggested the existence of a quaternary, rather than ternary, complex (XcpUH-VI-WJ-XK) at the tip of the pseudopilus. The assembly of this quaternary complex was further demonstrated by co-purification using affinity chromatography. Moreover, by testing various combinations of pseudopilins by surface plasmon resonance and affinity chromatography, we were able to dissect the different possible successive steps occurring during the formation of the quaternary complex. We propose a model in which XcpVI is the nucleator that first binds XcpXK and XcpWJ at different sites. Then the ternary complex recruits XcpUH through a direct interaction with XcpWJ. 相似文献