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71.
Cristina MeginoLuque Pol Sis Natalia MotaMartorell Raúl Navaridas Ins de la Rosa Izaskun Urdanibia Manel AlbertíValls Maria Santacana Miquel Pinyol Núria Bonifaci Anna Maci David LlobetNavas Snia Gatius Xavier MatiasGuiu Núria Eritja 《Molecular oncology》2022,16(11):2235
AT‐rich interactive domain‐containing protein 1A (ARID1A) loss‐of‐function mutation accompanied by a loss of ARID1A protein expression is frequently observed in endometrial carcinomas. However, the molecular mechanisms linking these genetic changes to the altered pathways regulating tumour initiation, maintenance and/or progression remain poorly understood. Thus, the main aim of this study was to analyse the role of ARID1A loss of function in endometrial tumorigenesis. Here, using different endometrial in vitro and in vivo models, such as tumoral cell lines, 3D primary cultures and metastatic or genetically modified mouse models, we show that altered expression of ARID1A is not enough to initiate endometrial tumorigenesis. However, in an established endometrial cancer context, ARID1A loss of function accelerates tumoral progression and metastasis through the disruption of the G2/M cell cycle checkpoint and ATM/ATR‐mediated DNA damage checkpoints, increases epithelial cell proliferation rates and induces epithelial mesenchymal transition through the activation of histone deacetylase 6 (HDAC6). Next, we demonstrated that the inhibition of HDAC6 function, using the HDAC6‐specific inhibitor ACY1215 or by transfection with HDAC6 short hairpin RNA (shRNA), can reverse the migratory and invasive phenotype of ARID1A‐knockdown cells. Further, we also show that inhibition of HDAC6 activity causes an apoptotic vulnerability to etoposide treatments in ARID1A‐deficient cells. In summary, the findings exposed in this work indicate that the inhibition of HDAC6 activity is a potential therapeutic strategy for patients suffering from ARID1A‐mutant endometrial cancer diagnosed in advanced stages. 相似文献
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Suarez D Ferrer R Artigas A Azkarate I Garnacho-Montero J Gomà G Levy MM Ruiz JC;Edusepsis Study Group 《Intensive care medicine》2011,37(3):444-452
Context
Severe sepsis is associated with high mortality and increased costs. The ‘Surviving Sepsis Campaign’ (SSC) protocol was developed as an international initiative to reduce mortality. However, its cost-effectiveness is unknown. 相似文献75.
76.
The goal of this study is to assess Ziziphus lotus’s potential for producing carboxymethylcellulose adsorption membranes with the ability to adsorb methyl green from wastewaters by the revalorization of its cellulosic fraction. The cellulose from this feedstock was extracted by an alkaline process and TAPPI standard technique T 203 cm-99 and afterwards they were carboxymethylated. The obtained carboxymethylcelluloses were deeply characterized, being observed that the carboxymethylcellulose produced from the alkaline cellulose presented the higher solubility due to its lower crystallinity degree (53.31 vs. 59.4%) and its higher substitution degree (0.85 vs. 0.74). This carboxymethylcellulose was cross-linked with citric acid in an aqueous treatment in order to form an adsorption membrane. The citric acid provided rigidity to the membrane and although it was hydrophilic it was not soluble in water. By evaluating the potential of the produced membrane for the removal of pollutant dyes from wastewater, it was observed that the adsorption membrane prepared from the carboxymethylcellulose’s produced from the Ziziphus lotus was able to remove 99% of the dye, methyl green, present in the wastewater. Thus, this work demonstrates the potential of the Ziziphus lotus for the production of a novel and cost-effective carboxymethylcellulose adsorption membrane with high capacity to treat wastewaters. 相似文献
77.
Jon Jatsu Azkue Jos Mara Mateos Izaskun Elezgarai Roco Bentez Esther Lzaro Peter Streit Pedro Grandes 《Brain research》1998,790(1-2):74-81
The midbrain periaqueductal gray is a key structure for the mediation of an integrated defence behaviour. Although a prominent role for glutamate in PAG mechanisms is supported by both behavioural and morphological studies, whether PAG afferents conveying somatosensory information constitute a source of glutamatergic input to the PAG remains unknown. Here, we have compared the projection pattern of orthogradely-labelled spinoannular fibres with the distribution of glutamate-like immunoreactivity in the PAG at the light microscopic level. Transaxonal labelling was observed throughout the whole rostrocaudal axis of the PAG except for the dorsolateral regions. Cell-processes and terminal-reminiscent puncta were strongly immunoreactive in all PAG regions, including the dorsolateral areas. To ascertain whether glutamate-immunoreactive puncta observed at light microscopy indeed constituted axon terminals of the spinoannular system, glutamate-like immunoreactivity was assessed in orthogradely-labelled synaptic terminals using a post-embedding immunogold procedure for electron microscopy. Quantitative analysis of gold particle densities revealed over twice as strong an immunoreactivity in anatomically-identified spinoannular axon terminals as in dendrites postsynaptic to them, perikarya and inhibitory Gray II synapses, as well as an over 5-fold heavier immunolabelling than in glial profiles. These findings reveal that glutamate is accumulated in synaptic terminals of the spinoannular system, supporting a neurotransmitter role for this acidic amino acid in spinofugal afferents to the PAG. 相似文献
78.
Izaskun Ibabe Judith A. Stein Adeline Nyamathi Peter M. Bentler 《Journal of substance abuse treatment》2014
The current study focuses on the relationships among a trauma history, a substance use history, chronic homelessness, and the mediating role of recent emotional distress in predicting drug treatment participation among adult homeless people. We explored the predictors of participation in substance abuse treatment because enrolling and retaining clients in substance abuse treatment programs is always a challenge particularly among homeless people. Participants were 853 homeless adults from Los Angeles, California. Using structural equation models, findings indicated that trauma history, substance use history and chronicity of homelessness were associated, and were significant predictors of greater recent emotional distress. The most notable result was that recent emotional distress predicted less participation in current substance abuse treatment (both formal and self-help) whereas a substance use history alone predicted significantly more participation in treatment. Implications concerning treatment engagement and difficulties in obtaining appropriate dual-diagnosis services for homeless mentally distressed individuals are discussed. 相似文献
79.
CYP3A5*3 and CYP3A4*1B allele distribution and genotype combinations: differences between Spaniards and Central Americans 总被引:1,自引:0,他引:1
Sinues B Vicente J Fanlo A Vasquez P Medina JC Mayayo E Conde B Arenaz I Martinez-Jarreta B 《Therapeutic drug monitoring》2007,29(4):412-416
The aim of this study was to detect genotypic differences between three populations of healthy volunteers from Northern Spain (204 subjects), Nicaragua (120 subjects), and El Salvador (112 subjects) regarding CYP3A4*1B and CYP3A5*3 polymorphisms. No significant differences were found by comparing allelic frequencies between the two Central American populations. The CYP3A5*3 allele frequency was significantly different (P < 0.01) between Central Americans (76%) and Spaniards (91%). By contrast, CYP3A4*1B allele was more prevalent among Central Americans (12.5%) than among North Spaniards (4%) (P < 0.01). Analysis of CYP3A4-3A5 genotype combinations revealed that individuals carrying CYP3A4*1B/CYP3A5*1 were more represented in Central Americans (16.9%) than in Spaniards (5.4%), suggesting a marked linkage disequilibrium. These data are compatible with a higher CYP3A enzyme activity in Central Americans as opposed to Spaniards and other white groups, which could imply differences in dose requirements for drugs metabolized by CYP3A and should be considered in allele-disease association studies. 相似文献
80.
Zorita I Ortiz-Zarragoitia M Soto M Cajaraville MP 《Aquatic toxicology (Amsterdam, Netherlands)》2006,78(Z1):S109-S116
In the present work, mussels (Mytilus edulis) were transplanted into a copper (Cu) gradient in Visnes (Norway) for a period of 3 weeks during November 2003. Sites 1 and 2 showed similar low levels of Cu, site 3 had intermediate Cu levels and site 4 was the most polluted with Cu as confirmed by AAS of digestive gland tissue. Values of lysosomal membrane labilization period were significantly lower at sites 3 and 4 compared to sites 1 and 2. The volume density and size of lysosomes was significantly decreased at site 4. The volume density of neutral lipids was also significantly lower at site 4 compared with the rest of sites. The volume density of lipofuscins showed significantly higher values at sites 2 and 3 compared to the reference site 1. Similar results were obtained regarding bioavailable metal levels measured by autometallography. All together, results are indicative of exocytosis of metal-containing lysosomes and lipofuscins to the digestive tubule lumen in mussels from site 4. In fact, autometallographic metal deposits were detected in digestive tubule lumen, brown cells and stomach in site 4 mussels. In agreement, there was a loss of digestive cells in mussels from site 4 (atrophy of the digestive epithelium) and cell type replacement (diminished volume density of digestive cells and increased volume density of basophilic cells). In conclusion, selected biomarkers indicated that mussels transplanted to sites closest to the Cu mine showed significant differences in metal accumulation pattern and in organization of the digestive gland tissue. Finally, female mussels closest to the Cu mine showed advanced gametogenesis with higher gonad index and vitellogenin-like protein levels than mussels at sites 1 and 2. 相似文献