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71.
Shiva Kumar Angala Juan Manuel Belardinelli Emilie Huc-Claustre William H. Wheat 《Critical reviews in biochemistry and molecular biology》2014,49(5):361-399
AbstractTuberculosis (TB) remains the second most common cause of death due to a single infectious agent. The cell envelope of Mycobacterium tuberculosis (Mtb), the causative agent of the disease in humans, is a source of unique glycoconjugates and the most distinctive feature of the biology of this organism. It is the basis of much of Mtb pathogenesis and one of the major causes of its intrinsic resistance to chemotherapeutic agents. At the same time, the unique structures of Mtb cell envelope glycoconjugates, their antigenicity and essentiality for mycobacterial growth provide opportunities for drug, vaccine, diagnostic and biomarker development, as clearly illustrated by recent advances in all of these translational aspects. This review focuses on our current understanding of the structure and biogenesis of Mtb glycoconjugates with particular emphasis on one of the most intriguing and least understood aspect of the physiology of mycobacteria: the translocation of these complex macromolecules across the different layers of the cell envelope. It further reviews the rather impressive progress made in the last 10 years in the discovery and development of novel inhibitors targeting their biogenesis. 相似文献
72.
Systemic inflammatory response syndromes (SIRS) may be caused by both infectious and sterile insults, such as trauma, ischemia-reperfusion or burns. They are characterized by early excessive inflammatory cytokine production and the endogenous release of several toxic and damaging molecules. These are necessary to fight and resolve the cause of SIRS, but often end up progressively damaging cells and tissues, leading to life-threatening multiple organ dysfunction syndrome (MODS). As inflammasome-dependent cytokines such as interleukin-1β are critically involved in the development of MODS and death in SIRS, and ATP is an essential activator of inflammasomes in vitro, we decided to analyze the ability of ATP removal to prevent excessive tissue damage and mortality in a murine LPS-induced inflammation model. Our results indeed indicate an important pro-inflammatory role for extracellular ATP. However, the effect of ATP is not restricted to inflammasome activation at all. Removing extracellular ATP with systemic apyrase treatment not only prevented IL-1β accumulation but also the production of inflammasome-independent cytokines such as TNF and IL-10. In addition, ATP removal also prevented systemic evidence of cellular disintegration, mitochondrial damage, apoptosis, intestinal barrier disruption and even mortality. Although blocking ATP receptors with the broad-spectrum P2 purinergic receptor antagonist suramin imitated certain beneficial effects of apyrase treatment, it could not prevent morbidity or mortality at all. We conclude that removal of systemic extracellular ATP could be a valuable strategy to dampen systemic inflammatory damage and toxicity in SIRS. 相似文献
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Shiva Gholizadeh-Ghaleh Aziz Maryam Pashaiasl Khodadad Khodadadi Onuche Ocheje 《Journal of cellular biochemistry》2019,120(11):18550-18558
Petri dish cultured cells have for long provided scientists an aperture to understanding cell's behavior both in normal and disease states as well as in vitro and in vivo. But recent advances have brought to light how the architecture and composite nature of the immediate environment within which the cell is proliferated can profoundly influence its phenotypic features and functions, thus making obvious, limitations of the conventional two-dimensional cell culture despite it cost effectiveness. Fortunately, the transition to three-dimensional (3D) cell culture has occurred concurrently with expanded knowledge of nanoscience and materials, thereby lending significant impetus for innovative research. This review is focused on the application of nanoparticles in 3D stem cell breeding, recent trends and developments in medical sciences for improved drug delivery, and treatment approaches to some human diseases. We also reviewed prevailing challenges and concerns of nanotoxicity as it continues to impede and delay clinical applications as well the ongoing concerted and multidisciplinary efforts to overcome them. 相似文献
75.
Taban Baghfalaki Mojtaba Ganjali Damon Berridge 《Biometrical journal. Biometrische Zeitschrift》2013,55(6):844-865
Joint modeling of longitudinal data and survival data has been used widely for analyzing AIDS clinical trials, where a biological marker such as CD4 count measurement can be an important predictor of survival. In most of these studies, a normal distribution is used for modeling longitudinal responses, which leads to vulnerable inference in the presence of outliers in longitudinal measurements. Powerful distributions for robust analysis are normal/independent distributions, which include univariate and multivariate versions of the Student's t, the slash and the contaminated normal distributions in addition to the normal. In this paper, a linear‐mixed effects model with normal/independent distribution for both random effects and residuals and Cox's model for survival time are used. For estimation, a Bayesian approach using Markov Chain Monte Carlo is adopted. Some simulation studies are performed for illustration of the proposed method. Also, the method is illustrated on a real AIDS data set and the best model is selected using some criteria. 相似文献
76.
Ali SkZ Sandhya Vardharajula Sai Shiva Krishna Prasad Vurukonda 《Annals of microbiology》2018,68(6):331-349
Several mechanisms have been proposed for plant growth-promoting rhizobacteria (PGPR)-mediated drought stress tolerance in plants, but little is known about the molecular pathways involved in the drought tolerance promoted by PGPR. We, therefore, aim to study the differential gene response between Pseudomonas putida strain FBKV2 and maize interaction under drought stress using Illumina sequencing. RNA Seq libraries were generated from leaf tissue of maize seedlings with and without strain FBKV2 subjected to drought stress. The libraries were mapped with maize genome database for the identification of differentially expressed genes (DEGs). The expression studies confirmed the downregulation of ethylene biosynthesis (ET), abscisic acid (ABA) and auxin signaling, superoxide dismutase, catalase, and peroxidase in FBKV2-inoculated seedlings. On the other hand, genes involved in β-alanine and choline biosynthesis, heat shock proteins, and late embryogenesis abundant (LEA) proteins were upregulated, which could act as key elements in the drought tolerance conferred by P. putida strain FBKV2. Another remarkable expression was observed in genes encoding benzoxazinoid (BX) biosynthesis which act as the chemoattractant, which was further confirmed by gfp-labeled P. putida strain FBKV2 root colonization studies. Overall, these results indicate that secretion of BXs attracted P. putida strain FBKV2 resulted in root colonization and mediated drought tolerance by modulating metabolic, signaling, and stress-responsive genes. 相似文献
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Mokhtar Ganjali Koli 《Molecular membrane biology》2016,33(3-5):64-75
A molecular dynamics (MD) simulation with atomistic details was performed to examine the partitioning and transport behavior of moderately cytotoxic ionic liquids (ILs), namely choline bis(2-ethylhexyl) phosphate (CBEH), choline bis(2,4,4-trimethylpentyl) phosphinate (CTMP) and choline O,O-diethyl dithiophosphate (CDEP) in a fully hydrated dipalmitoylphosphatidylcholine (DPPC) bilayer in the fluid phase at 323?K. The structure of ILs was so selected to understand if the role of dipole and dispersion forces in the ILs distribution in the membrane can be possible. Several analyses including mass density, electrostatic potential, order parameter, diffusion coefficients and hydrogen bond formation, was carried out to determine the precise location of the anionic species inside the membrane. Moreover, the potential of the mean force (PMF) method was used to calculate free energy profile for transferring anionic species from the DPPC membrane into the bulk water. While less cytotoxic DEP is located within the bulk water, more cytotoxic TMP and BEH ILs were found to remain in the membrane and the energy barrier for crossing through the bilayer center of BEH was higher. Various ILs have no significant effect on P–N vector. The thickness of lipid bilayer decreased in all systems comprising ILs, while area per lipid increased. 相似文献