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941.
Reservoir interactions and disease emergence 总被引:1,自引:0,他引:1
Animal populations act as reservoirs for emerging diseases. In order for transmission to be self-sustaining, a pathogen must have a basic reproduction number R0>1. Following a founding transmission event from an animal reservoir to humans, a pathogen has not yet adapted to its new environment and is likely to have an R0<1. However, subsequent evolution may rescue the pathogen from extinction in its new host. Recent applications of branching process theory investigate how the emergence of a novel pathogen is influenced by the number and rates of intermediate evolutionary steps. In addition, repeated contacts between human and reservoir populations may promote pathogen emergence. This article extends a stepping-stone model of pathogen evolution to include reservoir interactions. We demonstrate that the probability of a founding event culminating in an emerged pathogen can be significantly influenced by ongoing reservoir interactions. While infrequent reservoir interactions do not change the probability of disease emergence, moderately frequent interactions can promote emergence by facilitating adaptation to humans. Frequent reservoir interactions promote emergence even with minimal adaptation to humans. Thus, these results warn against perpetuated interaction between humans and animal reservoirs, as occurs when there are ecological or environmental changes that bring humans into more frequent contact with animal reservoirs. 相似文献
942.
Mitochondrial Diseases: Therapeutic Approaches 总被引:1,自引:0,他引:1
Therapy of mitochondrial encephalomyopathies (defined restrictively as defects of the mitochondrial respiratory chain) is
woefully inadequate, despite great progress in our understanding of the molecular bases of these disorders. In this review,
we consider sequentially several different therapeutic approaches. Palliative therapy is dictated by good medical practice
and includes anticonvulsant medication, control of endocrine dysfunction, and surgical procedures. Removal of noxious metabolites
is centered on combating lactic acidosis, but extends to other metabolites. Attempts to bypass blocks in the respiratory chain
by administration of electron acceptors have not been successful, but this may be amenable to genetic engineering. Administration
of metabolites and cofactors is the mainstay of real-life therapy and is especially important in disorders due to primary
deficiencies of specific compounds, such as carnitine or coenzyme Q10. There is increasing interest in the administration
of reactive oxygen species scavengers both in primary mitochondrial diseases and in neurodegenerative diseases directly or
indirectly related to mitochondrial dysfunction. Aerobic exercise and physical therapy prevent or correct deconditioning and
improve exercise tolerance in patients with mitochondrial myopathies due to mitochondrial DNA (mtDNA) mutations. Gene therapy
is a challenge because of polyplasmy and heteroplasmy, but interesting experimental approaches are being pursued and include,
for example, decreasing the ratio of mutant to wild-type mitochondrial genomes (gene shifting), converting mutated mtDNA genes
into normal nuclear DNA genes (allotopic expression), importing cognate genes from other species, or correcting mtDNA mutations
with specific restriction endonucleases. Germline therapy raises ethical problems but is being considered for prevention of
maternal transmission of mtDNA mutations. Preventive therapy through genetic counseling and prenatal diagnosis is becoming
increasingly important for nuclear DNA-related disorders. Progress in each of these approaches provides some glimmer of hope
for the future, although much work remains to be done. 相似文献
943.
Prion diseases are thought to be caused by the misfolding of the ubiquitous neuronal membrane prion protein (PrP) through an unknown mechanism that may involve Cu(II) coordination to the PrP. Previous work has utilized Ni(II) as a diamagnetic probe for Cu(II) coordination [C.E. Jones, M. Klewpatinond, S.R. Abdelraheim, D.R. Brown, J.H. Viles, J. Mol. Biol. 346 (2005) 1393-1407]. Herein we investigate Ni(II) coordination to the PrP fragment PrP(93-114) (AcN-GGTHSQWNKPSKPKTNMKHMAG) at pH=10.0 by Ni K-edge X-ray absorption spectroscopy (XAS). We find that two equivalents of Ni(II) will coordinate to PrP(93-114) by UV/Vis titrations and mass spectrometry. Ni K-edge XAS data is consistent with Ni(II) ligated by five N/O based ligands (three N/O ligands at 2.01(2) Angstrom and two at 1.855(2) Angstrom). We were also able to locate a Ni-Ni vector at 3.1(1) Angstrom, which suggests the two Ni(II) centers are contained in a bis-mu-hydroxo dimer. We therefore suggest that Ni(II) may not be a suitable diamagnetic mimic for Cu(II) coordination within the PrP since differential coordination modes for the two metals exist. 相似文献
944.
Gonçalves MO Coutinho-Filho WP Pimenta FP Pereira GA Pereira JA Mattos-Guaraldi AL Hirata R 《Letters in applied microbiology》2007,44(5):488-494
AIMS: This investigation aimed to isolate enteric rods from subgingival sites of patients presenting chronic periodontitis lesions, and to assess antimicrobial resistance and expression of hydrolytic enzymes. METHODS AND RESULTS: Enterobacteriaceae were isolated from 20% patients, and assayed for antimicrobial susceptibility and hydrolytic enzymes with specificity to different substrates. Isolates comprised seven Enterobacter cloacae (43.75%), five Serratia marcescens (31.25%), one Klebsiella pneumoniae (6.25%), one Enterobacter aerogenes (6.25%), one Pantoea agglomerans (6.25%), and one Citrobacter freundii (6.25%). Gelatinase activity was observed for 75% strains; caseinase and elastase was produced by six and two strains, respectively. DNase, lecithinase and lipase were expressed by S. marcescens. Most of strains were resistant to ampicillin (93.75%) and amoxicillin/clavulanic acid (81.25%). The majority of strains were susceptible to cephalosporins and aztreonam. Enterobacteria remained susceptible to imipenem, streptomycin and fluoroquinolones. Resistance to gentamicin, amikacin, sulfamethoxazole/thrimethoprim, tetracycline, and chloramphenicol were also observed. Eight strains presented multiple drug resistance. CONCLUSIONS: Subgingival sites from periodontal diseases contain multi-resistant and hydrolytic enzyme-producing enterobacteria that may contribute to overall tissue destruction and spreading. SIGNIFICANCE AND IMPACT OF THE STUDY: Enterobacteria isolated from patients generally considered as healthy individuals poses periodontal diseases as reservoir for systemic infections particularly in immunocompromised and hospitalized hosts. 相似文献
945.
In their reductionist approach in unraveling phenomena inside the cell, scientists in recent times have focused attention
to mitochondria. An organelle with peculiar evolutionary history and organization, it is turning out to be an important cell
survival switch. Besides controlling bioenergetics of a cell it also has its own genetic machinery which codes 37 genes. It
is a major source of generation of reactive oxygen species, acts as a safety device against toxic increases of cytosolic Ca2+ and its membrane permeability transition is a critical control point in cell death. Redox status of mitochondria is important
in combating oxidative stress and maintaining membrane permeability. Importance of mitochondria in deciding the response of
cell to multiplicity of physiological and genetic stresses, inter-organelle communication, and ultimate cell survival is constantly
being unraveled and discussed in this review. Mitochondrial events involved in apoptosis and necrotic cell death, such as
activation of Bcl-2 family proteins, formation of permeability transition pore, release of cytochrome c and apoptosis inducing factors, activation of caspase cascade, and ultimate cell death is the focus of attention not only
for cell biologists, but also for toxicologists in unraveling stress responses. Mutations caused by ROS to mitochondrial DNA,
its inability to repair it completely and creation of a vicious cycle of mutations along with role of Bcl-2 family genes and
proteins has been implicated in many diseases where mitochondrial dysfunctions play a key role. New therapeutic approaches
toward targeting low molecular weight compounds to mitochondria, including antioxidants is a step toward nipping the stress
in the bud. 相似文献
946.
D. K. Das A. Al-Juwaiser S. S. George I. M. Francis S. S. Sathar Z. A. Sheikh A. Shaheen S. K. Pathan B. E. Haji J. George K. Kapila 《Cytopathology》2007,18(3):157-167
INTRODUCTION: Non-Hodgkin's lymphoma (NHL) is often complicated by pleural effusion and ascites. The present study is an attempt to categorize the lymphomatous effusions according to the WHO classification, using archival material. METHODS: May-Grünwald-Giemsa and Papanicolaou-stained smears of 31 lymphomatous effusion specimens were reviewed. Of these, detailed cytological assessment was done on 12 pleural effusions and ten ascitic fluid specimens from 22 patients using the WHO lymphoma classification system. Immunocytochemical studies were performed in 21 specimens. RESULTS: Based on cytomorphological features, the 22 lymphomatous effusion specimens were categorized into lymphoplasmacytoid lymphoma (1), follicle centre cell (FCC) grade-1 (centrocytic) lymphoma (3), FCC grade-2 (centrocytic-centroblastic) lymphoma (3), FCC grade-3 (centroblastic) lymphoma (4), large cell immunoblastic lymphoma (4), lymphoblastic lymphoma (2), anaplastic large cell lymphoma (3) and miscellaneous types (2). Immunocytochemically, the lymphoma cells were T-cell (positive for CD3) and B-cell type (CD20 positive) in five and six cases respectively. CONCLUSION: Cytological examination of pleural effusion and ascitic fluid samples, supported by immunocytochemical studies, may be useful for the classification of lymphomas under the WHO system. 相似文献
947.
Lee CI Yang Q Perrier V Baskakov IV 《Protein science : a publication of the Protein Society》2007,16(10):2166-2173
Previous studies identified several single-point mutants of the prion protein that displayed dominant-negative effects on prion replication. The dominant-negative effect was assumed to be mediated by protein X, an as-yet-unknown cellular cofactor that is believed to be essential for prion replication. To gain insight into the mechanism that underlies the dominant-negative phenomena, we evaluated the effect of the Q218K variant of full-length recombinant prion protein (Q218K rPrP), one of the dominant-negative mutants, on cell-free polymerization of wild-type rPrP into amyloid fibrils. We found that both Q218K and wild-type (WT) rPrPs were incorporated into fibrils when incubated as a mixture; however, the yield of polymerization was substantially decreased in the presence of Q218K rPrP. Furthermore, in contrast to fibrils produced from WT rPrP, the fibrils generated in the mixture of WT and Q218K rPrPs did not acquire the proteinase K-resistant core of 16 kDa that was shown previously to encompass residues 97-230 and was similar to that of PrP(Sc). Our studies demonstrate that the Q218K variant exhibits the dominant-negative effect in cell-free conversion in the absence of protein X, and that this effect is, presumably, mediated by physical interaction between Q218K and WT rPrP during the polymerization process. 相似文献
948.
Boucheron C Toumieux S Compain P Martin OR Ikeda K Asano N 《Carbohydrate research》2007,342(12-13):1960-1965
Examples of a new type of inhibitor of human beta-glucocerebrosidase based on imino-disaccharides as glycosylceramide mimetics have been synthesized by way of the glycosylation of 1-deoxynojirimycin derivatives with 2,3,4,6-tetra-O-acetyl-alpha-D-glucopyranosyl bromide. 相似文献
949.
《Médecine Nucléaire》2022,46(3):164-167
Graves’ disease is an autoimmune disorder of thyroid which is characterized by hyperthyroidism, diffuse goiter, ophthalmopathy. Due to the pathophysiological mechanism of the disease, the disease affects both thyroid lobes. Unilateral involvement of the thyroid gland in patients with Graves’ disease is a rare entity, which suggests a difference between the two thyroid lobes. Clarifying this phenomenon could be a line of research for a better understanding of the pathophysiology of Graves's disease. This entity must be known to the clinician in order to take it better and avoid misdiagnosis. Here we present two cases of Graves’ disease which had unilateral involvement of the thyroid gland and discuss the hypotheses explaining this observation. 相似文献
950.
Jan Engelstdter Nicole Z. Fortuna 《Evolution; international journal of organic evolution》2019,73(7):1330-1340
Parasites often jump to and become established in a new host species. There is much evidence that the probability of such host shifts decreases with increasing phylogenetic distance between donor and recipient hosts, but the consequences of such preferential host switching remain little explored. We develop a computational model to investigate the dynamics of parasite host shifts in the presence of this phylogenetic distance effect. In this model, a clade of parasites evolves on an evolving clade of host species where parasites can cospeciate with their hosts, switch to new hosts, speciate within hosts or become extinct. Our model predicts that host phylogenies are major determinants of parasite distributions across trees. In particular, we predict that trees consisting of few large clades of host species and those with fast species turnover should harbor more parasites than trees with many small clades and those that diversify more slowly. Within trees, large clades are predicted to exhibit a higher fraction of infected species than small clades. We discuss our results in the light of recent cophylogenetic studies in a wide range of host–parasite systems. 相似文献