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51.
Víctor M. Rivilla Izaskun Jimnez-Serra Jesús Martín-Pintado Carlos Briones Lucas F. Rodríguez-Almeida Fernando Rico-Villas Beln Tercero Shaoshan Zeng Laura Colzi Pablo de Vicente Sergio Martín Miguel A. Requena-Torres 《Proceedings of the National Academy of Sciences of the United States of America》2021,118(22)
Cell membranes are a key element of life because they keep the genetic material and metabolic machinery together. All present cell membranes are made of phospholipids, yet the nature of the first membranes and the origin of phospholipids are still under debate. We report here the presence of ethanolamine in space, OH, which forms the hydrophilic head of the simplest and second-most-abundant phospholipid in membranes. The molecular column density of ethanolamine in interstellar space is = (1.510.07), implying a molecular abundance with respect to of . Previous studies reported its presence in meteoritic material, but they suggested that it is synthesized in the meteorite itself by decomposition of amino acids. However, we find that the proportion of the molecule with respect to water in the interstellar medium is similar to the one found in the meteorite (). These results indicate that ethanolamine forms efficiently in space and, if delivered onto early Earth, could have contributed to the assembling and early evolution of primitive membranes.Life is based on three basic subsystems: a compartment, a metabolic machinery, and information-bearing molecules together with replication mechanisms (1, 2). Among these key elements, compartmentalization is a fundamental prerequisite in the process of the emergence and early evolution of life (3, 4). Indeed, cellular membranes encapsulate and protect the genetic material, as well as enable the metabolic activities within the cell. The membranes of all current cells are made of a bilayer of phospholipids (Fig. 1 A and B), which are composed of a polar hydrophilic head (an alcohol phosphate group combined with a head group such as ethanolamine [EtA], choline, or serine) and two nonpolar hydrophobic tails (hydrocarbon chains derived from fatty acids), as depicted in Fig. 1C.Open in a separate windowFig. 1.Structure of cellular membranes. (A) Schematic view of a cell. (B) Zoom-in view of the cell membrane, formed by a phospholipid bilayer. (C) Three-dimensional structure of the phospholipid PE, formed by a hydrophilic head composed of EtA, a phosphate group linked to glycerol, and two hydrophobic fatty-acid tails (black, red, blue, and white balls denote carbon, oxygen, nitrogen, and hydrogen atoms, respectively). (D) EtA, the molecular species detected in space and reported in this work.The process through which the first phospholipids were formed remains unknown. Initial work proposed that phospholipids could be synthesized under possible prebiotic conditions (5–7), but the availability of the precursor molecules on early Earth was questioned (3, 8). Alternatively, the building blocks of phospholipids could have been delivered from space. A broad repertoire of prebiotic molecules could have been provided to the early Earth through the bombardment of comets and meteorites (9, 10). Laboratory impact experiments (11, 12) have demonstrated that a significant fraction of the prebiotic molecules in comets and meteorites can survive both passage through the planetary atmosphere and the impact on the surface.In particular, some structural parts of phospholipids are known to be present in meteorites, such as fatty acids, alcohols, and phosphonic acids (10, 13, 14). The glycerol phosphate group has been shown to be synthesized in irradiation experiments of interstellar ice analogs (15, 16), which supports the idea that they can form in space. Regarding the different head groups of phospholipids, EtA (also known as glycinol or 2-aminoethanol, OH; Fig. 1D) is the simplest one, and it forms the second-most-abundant phospholipid in biological membranes: phosphatidylethanolamine (PE) (see Fig. 1C). In addition, EtA has been proposed as a direct precursor of the simplest amino acid, glycine (COOH), in simulated archean alkaline hydrothermal vents (17), considered as one of the likely environments for the origin of life (18).EtA has been found in the Almahata Sitta meteorite (19), yet its origin is not known. A possible chemical formation route was proposed to be the thermal decomposition of amino acids under specific unusual conditions in the parent asteroid. This would limit the availability of EtA in the early Earth for the formation of phospholipids and thereafter of cell membranes. Another possibility is that EtA is formed from smaller interstellar precursors. However, the detection of EtA in the interstellar medium (ISM) has remained so far elusive (20). 相似文献
52.
Devon L. Graham Matthew A. Buendia Michelle A. Chapman Heather H. Durai Gregg D. Stanwood 《Synapse (New York, N.Y.)》2015,69(9):434-445
Gαq‐coupled receptors are ubiquitously expressed throughout the brain and body, and it has been shown that these receptors and associated signaling cascades are involved in a number of functional outputs, including motor function and learning and memory. Genetic alterations to Gαq have been implicated in neurodevelopmental disorders such as Sturge‐Weber syndrome. Some of these associated disease outcomes have been modeled in laboratory animals, but as Gαq is expressed in all cell types, it is difficult to differentiate the underlying circuitry or causative neuronal population. To begin to address neuronal cell type diversity in Gαq function, we utilized a conditional knockout mouse whereby Gαq was eliminated from telencephalic glutamatergic neurons. Unlike the global Gαq knockout mouse, we found that these conditional knockout mice were not physically different from control mice, nor did they exhibit any gross motor abnormalities. However, similarly to the constitutive knockout animal, Gαq conditional knockout mice demonstrated apparent deficits in spatial working memory. Loss of Gαq from glutamatergic neurons also produced enhanced sensitivity to cocaine‐induced locomotion, suggesting that cortical Gαq signaling may limit behavioral responses to psychostimulants. Screening for a variety of markers of forebrain neuronal architecture revealed no obvious differences in the conditional knockouts, suggesting that the loss of Gαq in telencephalic excitatory neurons does not result in major alterations in brain structure or neuronal differentiation. Taken together, our results define specific modulation of spatial working memory and psychostimulant responses through disruptions in Gαq signaling within cerebral cortical glutamatergic neurons. Synapse 69:434–445, 2015. © 2015 Wiley Periodicals, Inc. 相似文献
53.
Kosuke Hashimoto Ana Maria Suzuki Alexandre Dos Santos Christophe Desterke Agnese Collino Serena Ghisletti Emilie Braun Alessandro Bonetti Alexandre Fort Xian-Yang Qin Enrico Radaelli Bogumil Kaczkowski Alistair R.R. Forrest Soichi Kojima Didier Samuel Gioacchino Natoli Marie Annick Buendia Jamila Faivre Piero Carninci 《Genome research》2015,25(12):1812-1824
54.
Cairo S Wang Y de Reyniès A Duroure K Dahan J Redon MJ Fabre M McClelland M Wang XW Croce CM Buendia MA 《Proceedings of the National Academy of Sciences of the United States of America》2010,107(47):20471-20476
Myc activation has been implicated in the pathogenesis of hepatoblastoma (HB), a rare embryonal neoplasm derived from liver progenitor cells. Here, microRNA (miR) expression profiling of 65 HBs evidenced differential patterns related to developmental stage and Myc activity. Undifferentiated aggressive HBs overexpressed the miR-371-3 cluster with concomitant down-regulation of the miR-100/let-7a-2/miR-125b-1 cluster, evoking an ES cell expression profile. ChIP and Myc inhibition assays in hepatoma cells demonstrated that both miR clusters are regulated by Myc in an opposite manner. We show that the two miR clusters exert antagonistic effects on cell proliferation and tumorigenicity. Moreover, their combined deregulation cooperated in modulating the hepatic tumor phenotype, implicating stem cell-like regulation of Myc-dependent miRs in poorly differentiated HBs. Importantly, a four-miR signature representative of these clusters efficiently stratified HB patients, and when applied to 241 hepatocellular carcinomas (HCCs), it identified invasive tumors with a poor prognosis. Our data argue that Myc-driven reprogramming of miR expression patterns contributes to the aggressive phenotype of liver tumors originating from hepatic progenitor cells. 相似文献
55.
Garcia-Marcos L Canflanca IM Garrido JB Varela AL Garcia-Hernandez G Guillen Grima F Gonzalez-Diaz C Carvajal-Urueña I Arnedo-Pena A Busquets-Monge RM Morales Suarez-Varela M Blanco-Quiros A 《Thorax》2007,62(6):503-508
BACKGROUND: Although several studies have investigated the influence of diet on asthma in schoolchildren, none of them has evaluated how obesity can modify this effect. A study was undertaken to evaluate the association of various foods and a Mediterranean diet with the prevalence of asthma and rhinoconjunctivitis, adjusting for obesity and exercise. METHODS: A cross-sectional study was performed in 20 106 schoolchildren aged 6-7 years from eight Spanish cities. Using the ISAAC phase III questionnaire, parents reported chest and nose symptoms, food intake, weight, height and other factors, including exercise. A Mediterranean diet score was developed. A distinction was made between current occasional asthma (COA) and current severe asthma (CSA). RESULTS: Independent of the amount of exercise, each Mediterranean score unit had a small but protective effect on CSA in girls (adjusted OR 0.90, 95% CI 0.82 to 0.98). Exercise was a protective factor for COA and rhinoconjunctivitis in girls and boys (the more exercise, the more protection). Obesity was a risk factor for CSA in girls (adjusted OR 2.35, 95% CI 1.51 to 3.64). Individually, a more frequent intake (1-2 times/week and>or=3 times/week vs never/occasionally) of seafood (adjusted ORs 0.63 (95% CI 0.44 to 0.91) and 0.53 (95% CI 0.35 to 0.80)) and cereals (adjusted OR 0.56 (95% CI 0.30 to 1.02) and 0.39 (95% CI 0.23 to 0.68)) were protective factors for CSA, while fast food was a risk factor (adjusted ORs 1.64 (95% CI 1.28 to 2.10) and 2.26 (95% CI 1.09 to 4.68)). Seafood (adjusted ORs 0.74 (95% CI 0.60 to 0.92) and 0.67 (95% CI 0.53 to 0.85)) and fruit (adjusted ORs 0.76 (95% CI 0.60 to 0.97) and 0.71 (95% CI 0.57 to 0.88)) were protective factors for rhinoconjunctivitis. CONCLUSIONS: A Mediterranean diet has a potentially protective effect in girls aged 6-7 years with CSA. Obesity is a risk factor for this type of asthma only in girls. 相似文献
56.
Carmen Martinez Peinado M.D. Cristina Díaz de Heredia M.D. Jordi To‐Figueras M.D. Salvador Arias‐Santiago M.D. Paloma Nogueras M.D. Izaskun Elorza M.D. Teresa Olivé M.D. Célia Bádenas M.D. Mª José Moreno M.D. Jesús Tercedor M.D. Carmen Herrero M.D. Ph.D. 《Pediatric dermatology》2013,30(4):484-489
Congenital erythropoietic porphyria (CEP), or Günther's disease, is an inborn error of metabolism produced by a deficiency of uroporphyrinogen III synthase (UROS), the fourth enzyme of the heme biosynthesis pathway. This enzymatic defect induces the accumulation of isomer I porphyrins in erythrocytes, skin, and tissues, producing various clinical manifestations. Severe cases are characterized by extreme photosensitivity, causing scarring and mutilations, and by hemolytic anemia, reducing life expectancy. CEP is caused by mutations in the UROS gene, and one of the most severe forms of the disease is associated with a cysteine to arginine substitution at residue 73 of the protein (C73R). CEP has been successfully treated only by the transplantation of hematopoietic precursors. We report the case of a male infant with severe postdelivery symptoms diagnosed with CEP and found to be homozygous for the C73R mutation. He underwent successful allogeneic bone marrow transplantation from a matched unrelated donor at 7 months of age. The hemolytic anemia was corrected and the porphyrin overproduction was significantly reduced. The patient remained asymptomatic after 1 year. This new case confirms that patients with severe CEP can benefit from early postnatal hematopoietic stem cell transplantation. 相似文献
57.
58.
Hiart Maortua Cristina Martínez-Bouzas Ainhoa García-Ribes María-Jesus Martínez Encarna Guillen María-Rosario Domingo María-Teresa Calvo Miriam Guitart Elisabeth Gabau María-Pilar Botella Blanca Gener Izaskun Rubio María-Asunción López-Aríztegui María-Isabel Tejada 《The Journal of molecular diagnostics : JMD》2013,15(5):723-729
59.
Cavard C Terris B Grimber G Christa L Audard V Radenen-Bussiere B Simon MT Renard CA Buendia MA Perret C 《Oncogene》2006,25(4):599-608
The Wnt/beta-catenin signaling pathway is activated in many human hepatocellular carcinomas (HCC). We tried to identify the genes involved in carcinogenesis and progression of HCC with beta-catenin mutations. We used PCR-based subtractive hybridization to compare gene expression between malignant and benign components of a human HCC occurring in pre-existing adenoma activated for beta-catenin. Two of the genes identified belong to the Regenerating gene (REG) family. They encode the Regenerating islet-derived 3 alpha (REG3A/HIP/PAP/REG-III) and 1 alpha (REG1A) proteins, both involved in liver and pancreatic regeneration and proliferation. Using siRNA directed against beta-catenin, we demonstrated that REG3A is a target of beta-catenin signaling in Huh7 hepatoma cells. The upregulation of REG3A and REG1A expression is significantly correlated to the beta-catenin status in 42 HCC and 28 hepatoblastomas characterized for their beta-catenin status. Thus, we report strong evidence that both genes are downstream targets of the Wnt pathway during liver tumorigenesis. 相似文献
60.
Bilbao Acedos I March Cerdá JC Prieto Rodríguez MA 《Revista espa?ola de salud pública》2002,76(5):483-492
Qualitative methodology, originally belonging to the Social Sciences domain, has progressively incorporated to Health Research to the scepticism of many and the admiration of others. Nowadays, validity and fiability of these qualitative techniques is still questioned by a great amount of health researchers and their use provokes doubt among reviewers and other members of the scientific community. This article presents as a fundamental measure for the validity of the qualitative methodology its precise use to approach determinate research objectives specific to them and, echoing the extra issue of the Health Services Research on December 1999 on this methodology, gathers the contribution of the use of these techniques from a complementary point of view, in a Internal Communication Audit conducted in the Primary Care Services of four Regional Health Systems: Area II of the INSALUD (National Health Institute), Basque Health System, Canary Health System and Andalusian Health System. 相似文献