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101.
102.
White GE Cotterill A Addley MR Soilleux EJ Greaves DR 《Journal of molecular histology》2011,42(2):137-151
Treatment of cells with cytokines and growth factors leads to the synthesis of Suppressor of Cytokine Signalling (SOCS) proteins
that act as potent negative regulators of signalling via the Jak/STAT pathway. We used immunohistochemistry to identify cells
and pathologies where SOCS3 expression might influence acute and chronic inflammatory responses in human tissues. Epitope
and GFP tagged SOCS3 fusion proteins were localised predominantly in the nucleus of transfected cells and a validated anti
SOCS3 antiserum revealed the expression of SOCS3 in the nucleus and cytoplasm of macrophages, endothelial and epithelial cells
in a wide range of normal tissues in tissue microarrays (n = 31 different tissues). Nuclear SOCS3 was only seen in cells expressing a high level of the protein. Comparative immunostaining
of acute, chronically and granulomatously inflamed human tissues revealed higher levels of nuclear and cytoplasmic SOCS3 expression
in inflamed than in corresponding normal tissues, particularly in recruited leukocyte populations, but also in epithelia.
The staining appeared more intense, suggesting higher expression levels, in areas where inflammation was more acute, consistent
with the time course of SOCS3 induction described in vitro. Expression of SOCS3 protein by leucocytes and other cell types
in tissue sections could be a useful marker of cells undergoing acute or chronic stimulation by cytokines in vivo. 相似文献
103.
104.
Fookes M Schroeder GN Langridge GC Blondel CJ Mammina C Connor TR Seth-Smith H Vernikos GS Robinson KS Sanders M Petty NK Kingsley RA Bäumler AJ Nuccio SP Contreras I Santiviago CA Maskell D Barrow P Humphrey T Nastasi A Roberts M Frankel G Parkhill J Dougan G Thomson NR 《PLoS pathogens》2011,7(8):e1002191
The genus Salmonella contains two species, S. bongori and S. enterica. Compared to the well-studied S. enterica there is a marked lack of information regarding the genetic makeup and diversity of S. bongori. S. bongori has been found predominantly associated with cold-blooded animals, but it can infect humans. To define the phylogeny of this species, and compare it to S. enterica, we have sequenced 28 isolates representing most of the known diversity of S. bongori. This cross-species analysis allowed us to confidently differentiate ancestral functions from those acquired following speciation, which include both metabolic and virulence-associated capacities. We show that, although S. bongori inherited a basic set of Salmonella common virulence functions, it has subsequently elaborated on this in a different direction to S. enterica. It is an established feature of S. enterica evolution that the acquisition of the type III secretion systems (T3SS-1 and T3SS-2) has been followed by the sequential acquisition of genes encoding secreted targets, termed effectors proteins. We show that this is also true of S. bongori, which has acquired an array of novel effector proteins (sboA-L). All but two of these effectors have no significant S. enterica homologues and instead are highly similar to those found in enteropathogenic Escherichia coli (EPEC). Remarkably, SboH is found to be a chimeric effector protein, encoded by a fusion of the T3SS-1 effector gene sopA and a gene highly similar to the EPEC effector nleH from enteropathogenic E. coli. We demonstrate that representatives of these new effectors are translocated and that SboH, similarly to NleH, blocks intrinsic apoptotic pathways while being targeted to the mitochondria by the SopA part of the fusion. This work suggests that S. bongori has inherited the ancestral Salmonella virulence gene set, but has adapted by incorporating virulence determinants that resemble those employed by EPEC. 相似文献
105.
Plants and microbes produce multiple carotenoid pigments with important nutritional roles in animals. By unraveling the basis of carotenoid biosynthesis it has become possible to modulate the key metabolic steps in plants and thus increase the nutritional value of staple crops, such as rice (Oryza sativa), maize (Zea mays) and potato (Solanum tuberosum). Multigene engineering has been used to modify three different metabolic pathways simultaneously, producing maize seeds with higher levels of carotenoids, folate and ascorbate. This strategy may allow the development of nutritionally enhanced staples providing adequate amounts of several unrelated nutrients. By focusing on different steps in the carotenoid biosynthesis pathway, it is also possible to generate plants with enhanced levels of several nutritionally-beneficial carotenoid molecules simultaneously. 相似文献
106.
Natural enemies, especially host-specific enemies, are hypothesised to facilitate the coexistence of plant species by disproportionately inflicting more damage at increasing host abundance. However, few studies have assessed such Janzen-Connell mechanisms on a scale relevant for coexistence and no study has evaluated potential top-down influences on the specialized pests. We quantified seed predation by specialist invertebrates and generalist vertebrates, as well as larval predation on these invertebrates, for the Neotropical palm Attalea butyracea across ten 4-ha plots spanning 20-fold variation in palm density. As palm density increased, seed attack by bruchid beetles increased, whereas seed predation by rodents held constant. But because rodent predation on bruchid larvae increased disproportionately with increasing palm density, bruchid emergence rates and total seed predation by rodents and bruchids combined were both density-independent. Our results demonstrate that top-down effects can limit the potential of host-specific insects to induce negative-density dependence in plant populations. 相似文献
107.
There is a paucity of chemical matter suitably poised for effective drug development. Improving the quality and efficiency of research early on in the drug discovery process has been a long standing objective for the drug industry and improvements to the accessibility and quality of compound screening decks might have a significant and positive impact. In the absence of specific molecular information that can be modeled and used predicatively we are far from identifying which small molecules are most relevant to emerging biological targets such as protein-protein interactions. Natural products have been historically successful as an entry point for drug discovery and recently screening libraries are being synthesized to emulate natural product like features. 相似文献
108.
Beck CR McKenzie BC Hashim AB Harris RC Zanuzdana A Agboado G Orton E Béchard-Evans L Morgan G Stevenson C Weston R Mukaigawara M Enstone J Augustine G Butt M Kim S Puleston R Dabke G Howard R O'Boyle J O'Brien M Ahyow L Denness H Farmer S Figureroa J Fisher P Greaves F Haroon M Haroon S Hird C Isba R Ishola DA Kerac M Parish V Roberts J Rosser J Theaker S Wallace D Wigglesworth N Lingard L Vinogradova Y Horiuchi H Peñalver J Nguyen-Van-Tam JS 《PloS one》2011,6(12):e29249
Background
Immunocompromised patients are vulnerable to severe or complicated influenza infection. Vaccination is widely recommended for this group. This systematic review and meta-analysis assesses influenza vaccination for immunocompromised patients in terms of preventing influenza-like illness and laboratory confirmed influenza, serological response and adverse events.Methodology/Principal Findings
Electronic databases and grey literature were searched and records were screened against eligibility criteria. Data extraction and risk of bias assessments were performed in duplicate. Results were synthesised narratively and meta-analyses were conducted where feasible. Heterogeneity was assessed using I2 and publication bias was assessed using Begg''s funnel plot and Egger''s regression test. Many of the 209 eligible studies included an unclear or high risk of bias. Meta-analyses showed a significant effect of preventing influenza-like illness (odds ratio [OR] = 0.23; 95% confidence interval [CI] = 0.16–0.34; p<0.001) and laboratory confirmed influenza infection (OR = 0.15; 95% CI = 0.03–0.63; p = 0.01) through vaccinating immunocompromised patie nts compared to placebo or unvaccinated controls. We found no difference in the odds of influenza-like illness compared to vaccinated immunocompetent controls. The pooled odds of seroconversion were lower in vaccinated patients compared to immunocompetent controls for seasonal influenza A(H1N1), A(H3N2) and B. A similar trend was identified for seroprotection. Meta-analyses of seroconversion showed higher odds in vaccinated patients compared to placebo or unvaccinated controls, although this reached significance for influenza B only. Publication bias was not detected and narrative synthesis supported our findings. No consistent evidence of safety concerns was identified.Conclusions/Significance
Infection prevention and control strategies should recommend vaccinating immunocompromised patients. Potential for bias and confounding and the presence of heterogeneity mean the evidence reviewed is generally weak, although the directions of effects are consistent. Areas for further research are identified. 相似文献109.
Enzymes are basically composed of 20 naturally occurring amino acids, yet they catalyse a dizzying array of chemical reactions, with regiospecificity and stereospecificity and under physiological conditions. In this review, we attempt to gain some understanding of these complex proteins, from the chemical versatility of the catalytic toolkit, including the use of cofactors (both metal ions and organic molecules), to the complex mapping of reactions to proteins (which is rarely one-to-one), and finally the structural complexity of enzymes and their active sites, often involving multidomain or multisubunit assemblies. This work highlights how the enzymes that we see today reflect millions of years of evolution, involving de novo design followed by exquisite regulation and modulation to create optimal fitness for life. 相似文献
110.
Expression of the Bacillus thuringiensis Mosquitocidal Toxin Cry11Aa in the Aquatic Bacterium Asticcacaulis excentricus 总被引:2,自引:0,他引:2
A mosquitocidal aquatic bacterium has been developed by introducing an operon containing the cry11Aa, and p20 genes from Bacillus thuringiensis subsp. israelensis (Bti) into the gram-negative aquatic bacterium Asticcacaulis excentricus. After transformation, the cry11Aa gene was successfully expressed in recombinant A. excentricus under the tac promoter, at the level of 0.04 pg/cell. The recombinant bacteria were toxic to Aedes aegypti larvae with an LC50 of 6.83 × 105 cells/mL. We believe that these bacteria may have potential as genetically engineered microorganisms for the control of mosquito
larvae. 相似文献