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851.
Steven J. Hancock Alvin W. Lo Thomas Ve Christopher J. Day Lendl Tan Alejandra A. Mendez Minh-Duy Phan Nguyen Thi Khanh Nhu Kate M. Peters Amanda C. Richards Brittany A. Fleming Chyden Chang Dalton H. Y. Ngu Brian M. Forde Thomas Haselhorst Kelvin G. K. Goh Scott A. Beatson Michael P. Jennings Matthew A. Mulvey Bostjan Kobe Mark A. Schembri 《PLoS pathogens》2022,18(6)
Extra-intestinal pathogenic Escherichia coli (ExPEC) belong to a critical priority group of antibiotic resistant pathogens. ExPEC establish gut reservoirs that seed infection of the urinary tract and bloodstream, but the mechanisms of gut colonisation remain to be properly understood. Ucl fimbriae are attachment organelles that facilitate ExPEC adherence. Here, we investigated cellular receptors for Ucl fimbriae and Ucl expression to define molecular mechanisms of Ucl-mediated ExPEC colonisation of the gut. We demonstrate differential expression of Ucl fimbriae in ExPEC sequence types associated with disseminated infection. Genome editing of strains from two common sequence types, F11 (ST127) and UTI89 (ST95), identified a single nucleotide polymorphism in the ucl promoter that changes fimbriae expression via activation by the global stress-response regulator OxyR, leading to altered gut colonisation. Structure-function analysis of the Ucl fimbriae tip-adhesin (UclD) identified high-affinity glycan receptor targets, with highest affinity for sialyllacto-N-fucopentose VI, a structure likely to be expressed on the gut epithelium. Comparison of the UclD adhesin to the homologous UcaD tip-adhesin from Proteus mirabilis revealed that although they possess a similar tertiary structure, apart from lacto-N-fucopentose VI that bound to both adhesins at low-micromolar affinity, they recognize different fucose- and glucose-containing oligosaccharides. Competitive surface plasmon resonance analysis together with co-structural investigation of UcaD in complex with monosaccharides revealed a broad-specificity glycan binding pocket shared between UcaD and UclD that could accommodate these interactions. Overall, our study describes a mechanism of adaptation that augments establishment of an ExPEC gut reservoir to seed disseminated infections, providing a pathway for the development of targeted anti-adhesion therapeutics. 相似文献
852.
Samuel L. Freeman Vera Skafar Hanna Kwon Alistair J. Fielding Peter C.E. Moody Alejandra Martínez Federico M. Issoglio Lucas Inchausti Pablo Smircich Ari Zeida Lucía Piacenza Rafael Radi Emma L. Raven 《The Journal of biological chemistry》2022,298(8)
The protozoan parasite Trypanosoma cruzi is the causative agent of American trypanosomiasis, otherwise known as Chagas disease. To survive in the host, the T. cruzi parasite needs antioxidant defense systems. One of these is a hybrid heme peroxidase, the T. cruzi ascorbate peroxidase-cytochrome c peroxidase enzyme (TcAPx-CcP). TcAPx-CcP has high sequence identity to members of the class I peroxidase family, notably ascorbate peroxidase (APX) and cytochrome c peroxidase (CcP), as well as a mitochondrial peroxidase from Leishmania major (LmP). The aim of this work was to solve the structure and examine the reactivity of the TcAPx-CcP enzyme. Low temperature electron paramagnetic resonance spectra support the formation of an exchange-coupled [Fe(IV)=O Trp233•+] compound I radical species, analogous to that used in CcP and LmP. We demonstrate that TcAPx-CcP is similar in overall structure to APX and CcP, but there are differences in the substrate-binding regions. Furthermore, the electron transfer pathway from cytochrome c to the heme in CcP and LmP is preserved in the TcAPx-CcP structure. Integration of steady state kinetic experiments, molecular dynamic simulations, and bioinformatic analyses indicates that TcAPx-CcP preferentially oxidizes cytochrome c but is still competent for oxidization of ascorbate. The results reveal that TcAPx-CcP is a credible cytochrome c peroxidase, which can also bind and use ascorbate in host cells, where concentrations are in the millimolar range. Thus, kinetically and functionally TcAPx-CcP can be considered a hybrid peroxidase. 相似文献
853.
854.
Beatriz Armida Flores-Lpez María de la Luz Ayala-Madrigal Jos Miguel Moreno-Ortiz Jorge Peregrina-Sandoval Miguel ngel Trujillo-Rojas Jos Luis Venegas-Rodríguez Rosario Hernndez-Ramírez Martha Alejandra Fernndez-Galindo Melva Gutirrez-Angulo 《Current issues in molecular biology》2022,44(8):3770
Colorectal cancer is a heterogeneous disease with multiple genomic changes that influence the clinical management of patients; thus, the search for new molecular targets remains necessary. The aim of this study was to identify genetic variants in tumor tissues from Mexican patients with colorectal cancer, using massive parallel sequencing. A total of 4813 genes were analyzed in tumoral DNA from colorectal cancer patients, using the TruSight One Sequencing panel. From these, 192 variants with clinical associations were found distributed in 168 different genes, of which 46 variants had not been previous reported in the literature or databases, although genes harboring those variants had already been described in colorectal cancer. Enrichment analysis of the affected genes was performed using Reactome software; pathway over-representation showed significance for disease, signal transduction, and immune system subsets in all patients, while exclusive subsets such as DNA repair, autophagy, and RNA metabolism were also found. Those characteristics, whether individual or shared, could give tumors specific capabilities for survival, aggressiveness, or response to treatment. Our results can be useful for future investigations targeting specific characteristics of tumors in colorectal cancer patients. The identification of exclusive or common pathways in colorectal cancer patients could be important for better diagnosis and personalized cancer treatment. 相似文献
855.
Alejandra Laguillo-Diego Robert Kiewisz Carlos Martí-Gmez Daniel Baum Thomas Müller-Reichert Isabelle Vernos 《Molecular biology of the cell》2023,34(1)
Faithful chromosome segregation requires the assembly of a bipolar spindle, consisting of two antiparallel microtubule (MT) arrays having most of their minus ends focused at the spindle poles and their plus ends overlapping in the spindle midzone. Spindle assembly, chromosome alignment, and segregation require highly dynamic MTs. The plus ends of MTs have been extensively investigated but their minus-end structure remains poorly characterized. Here, we used large-scale electron tomography to study the morphology of the MT minus ends in three dimensionally reconstructed metaphase spindles in HeLa cells. In contrast to the homogeneous open morphology of the MT plus ends at the kinetochores, we found that MT minus ends are heterogeneous, showing either open or closed morphologies. Silencing the minus end–specific stabilizer, MCRS1 increased the proportion of open MT minus ends. Altogether, these data suggest a correlation between the morphology and the dynamic state of the MT ends. Taking this heterogeneity of the MT minus-end morphologies into account, our work indicates an unsynchronized behavior of MTs at the spindle poles, thus laying the groundwork for further studies on the complexity of MT dynamics regulation. 相似文献
856.
Paula Roca-Saavedra Veronica Mendez-Vilabrille Jose Manuel Miranda Carolina Nebot Alejandra Cardelle-Cobas Carlos M. Franco Alberto Cepeda 《Journal of physiology and biochemistry》2018,74(1):69-83
Gut bacteria play an important role in several metabolic processes and human diseases, such as obesity and accompanying co-morbidities, such as fatty liver disease, insulin resistance/diabetes, and cardiovascular events. Among other factors, dietary patterns, probiotics, prebiotics, synbiotics, antibiotics, and non-dietary factors, such as stress, age, exercise, and climatic conditions, can dramatically impact the human gut microbiota equilibrium and diversity. However, the effect of minor food constituents, including food additives and trace contaminants, on human gut microbiota has received less attention. Consequently, the present review aimed to provide an objective perspective of the current knowledge regarding the impacts of minor food constituents on human gut microbiota and consequently, on human health. 相似文献
857.
858.
The objective of this study was to describe the morphological and anatomical features of five unidentified ectomycorrhizal types of Alnus acuminata and to complement their identification based on ITS-rDNA sequence analysis. The combined approach of morphotyping and sequence analysis based on ITS sequence comparison with sequences contained in GenBank and the UNITE database let us assign three of the five field-collected ectomycorrhiza morphotypes to the tomentella-thelephora lineage that closely matched European and North American species. The sequencing results within Tomentella point toward alder specific clades within T. sublilacina, T. ellisii and T. stuposa sensu lato. The two other EcM morphotypes matched Lactarius omphaliiformis and a Russula sp. Better focused, concomitant fruit body surveys are needed for accurate identification of South American ectomycorrhizal fungi because of the evidence of cryptic speciation in both agaricoid and resupinate mycobionts. 相似文献
859.
Anaya-López JL López-Meza JE Baizabal-Aguirre VM Cano-Camacho H Ochoa-Zarzosa A 《Biotechnology letters》2006,28(14):1101-1108
Plant defensins are antimicrobial peptides that exhibit mainly antifungal activity against a broad range of plant fungal pathogens. However, their actions against Candida albicans have not been extensively studied. The mRNA for γ-thionin, a defensin from Capsicum chinense, has been expressed in bovine endothelial cells. The conditioned medium of these cells showed antifungal activity on germ tube formation (60–70% of inhibition) and on the viability of C. albicans (70–80% of inhibition). Additionally, C. albicans was not able to penetrate transfected cells. Conditioned medium from these cells also inhibited the viability (80%) of the human tumor cell line, HeLa. 相似文献
860.
Juan David Medina Laura Alejandra Osorio Daniel Zabala Ricardo Wagner de Almeida Vitor Jorge Enrique Gmez Julio Csar Carranza Gustavo Adolfo Vallejo 《Biomédica : revista del Instituto Nacional de Salud》2022,42(1):136