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161.
162.
Samuel Plante Rapha?l Ioannoni Jude Beaudoin Simon Labbé 《The Journal of biological chemistry》2014,289(14):10168-10181
Meiosis requires copper to undertake its program in which haploid gametes are produced from diploid precursor cells. In Schizosaccharomyces pombe, copper is transported by three members of the copper transporter (Ctr) family, namely Ctr4, Ctr5, and Ctr6. Although central for sexual differentiation, very little is known about the expression profile, cellular localization, and physiological contribution of the Ctr proteins during meiosis. Analysis of gene expression of ctr4+ and ctr5+ revealed that they are primarily expressed in early meiosis under low copper conditions. In the case of ctr6+, its expression is broader, being detected throughout the entire meiotic process with an increase during middle- and late-phase meiosis. Whereas the expression of ctr4+ and ctr5+ is exclusively dependent on the presence of Cuf1, ctr6+ gene expression relies on two distinct regulators, Cuf1 and Mei4. Ctr4 and Ctr5 proteins co-localize at the plasma membrane shortly after meiotic induction, whereas Ctr6 is located on the membrane of vacuoles. After meiotic divisions, Ctr4 and Ctr5 disappear from the cell surface, whereas Ctr6 undergoes an intracellular re-location to co-localize with the forespore membrane. Under copper-limiting conditions, disruption of ctr4+ and ctr6+ results in altered SOD1 activity, whereas these mutant cells exhibit substantially decreased levels of CAO activity mostly in early- and middle-phase meiosis. Collectively, these results emphasize the notion that Ctr proteins exhibit differential expression, localization, and contribution in delivering copper to SOD1 and Cao1 proteins during meiosis. 相似文献
163.
Approaches to conserving natural enemy populations in greenhouse crops: current methods and future prospects 总被引:1,自引:0,他引:1
Gerben J. Messelink Jude Bennison Oscar Alomar Barbara L. Ingegno Luciana Tavella Les Shipp Eric Palevsky Felix L. Wäckers 《BioControl》2014,59(4):377-393
Biological pest control in greenhouse crops is usually based on periodical releases of mass-produced natural enemies, and this method has been successfully applied for decades. However, in some cases there are shortcomings in pest control efficacy, which often can be attributed to the poor establishment of natural enemies. Their establishment and population numbers can be enhanced by providing additional resources, such as alternative food, prey, hosts, oviposition sites or shelters. Furthermore, natural enemy efficacy can be enhanced by using volatiles, adapting the greenhouse climate, avoiding pesticide side-effects and minimizing disrupting food web complexities. The special case of high value crops in a protected greenhouse environment offers tremendous opportunities to design and manage the system in ways that increase crop resilience to pest infestations. While we have outlined opportunities and tools to develop such systems, this review also identifies knowledge gaps, where additional research is needed to optimize these tools. 相似文献
164.
165.
Ranjan Ramasamy Pavilupillai J. Jude Thabothiny Veluppillai Thampoe Eswaramohan Sinnathamby N. Surendran 《PloS one》2014,9(8)
The mainly fresh water arboviral vector Aedes aegypti L. (Diptera: Culicidae) can also undergo pre-imaginal development in brackish water of up to 15 ppt (parts per thousand) salt in coastal areas. We investigated differences in salinity tolerance, egg laying preference, egg hatching and larval development times and resistance to common insecticides in Ae. aegypti collected from brackish and fresh water habitats in Jaffna, Sri Lanka. Brackish water-derived Ae. aegypti were more tolerant of salinity than fresh water-derived Ae. aegypti and this difference was only partly reduced after their transfer to fresh water for up to five generations. Brackish water-derived Ae. aegypti did not significantly discriminate between 10 ppt salt brackish water and fresh water for oviposition, while fresh water-derived Ae. aegypti preferred fresh water. The hatching of eggs from both brackish and fresh water-derived Ae. aegypti was less efficient and the time taken for larvae to develop into pupae was prolonged in 10 ppt salt brackish water. Ae. aegypti isolated from coastal brackish water were less resistant to the organophosphate insecticide malathion than inland fresh water Ae. aegypti. Brackish and fresh water-derived Ae. aegypti however were able to mate and produce viable offspring in the laboratory. The results suggest that development in brackish water is characterised by pertinent biological changes, and that there is restricted genetic exchange between coastal brackish and inland fresh water Ae. aegypti isolates from sites 5 km apart. The findings highlight the need for monitoring Ae. aegypti developing in coastal brackish waters and extending vector control measures to their habitats. 相似文献
166.
Angel E. Dago Asya Stepansky Anders Carlsson Madelyn Luttgen Jude Kendall Timour Baslan Anand Kolatkar Michael Wigler Kelly Bethel Mitchell E. Gross James Hicks Peter Kuhn 《PloS one》2014,9(8)
Timely characterization of a cancer''s evolution is required to predict treatment efficacy and to detect resistance early. High content analysis of single Circulating Tumor Cells (CTCs) enables sequential characterization of genotypic, morphometric and protein expression alterations in real time over the course of cancer treatment. This concept was investigated in a patient with castrate-resistant prostate cancer progressing through both chemotherapy and targeted therapy. In this case study, we integrate across four timepoints 41 genome-wide copy number variation (CNV) profiles plus morphometric parameters and androgen receptor (AR) protein levels. Remarkably, little change was observed in response to standard chemotherapy, evidenced by the fact that a unique clone (A), exhibiting highly rearranged CNV profiles and AR+ phenotype was found circulating before and after treatment. However, clinical response and subsequent progression after targeted therapy was associated with the drastic depletion of clone A, followed by the sequential emergence of two distinct CTC sub-populations that differed in both AR genotype and expression phenotype. While AR- cells with flat or pseudo-diploid CNV profiles (clone B) were identified at the time of response, a new tumor lineage of AR+ cells (clone C) with CNV altered profiles was detected during relapse. We showed that clone C, despite phylogenetically related to clone A, possessed a unique set of somatic CNV alterations, including MYC amplification, an event linked to hormone escape. Interesting, we showed that both clones acquired AR gene amplification by deploying different evolutionary paths. Overall, these data demonstrate the timeframe of tumor evolution in response to therapy and provide a framework for the multi-scale analysis of fluid biopsies to quantify and monitor disease evolution in individual patients. 相似文献
167.
Jude Igumbor Sophie Pascoe Shuabe Rajap Wendy Townsend John Sargent Ernest Darkoh 《PloS one》2014,9(10)
Introduction
The increasing number of people requiring HIV treatment in South Africa calls for efficient use of its human resources for health in order to ensure optimum treatment coverage and outcomes. This paper describes an innovative public-private partnership model which uses private sector doctors to treat public sector patients and ascertains the model’s ability to maintain treatment outcomes over time.Methods
The study used a retrospective design based on the electronic records of patients who were down-referred from government hospitals to selected private general medical practitioners (GPs) between November 2005 and October 2012. In total, 2535 unique patient records from 40 GPs were reviewed. The survival functions for mortality and attrition were calculated. Cumulative incidence of mortality for different time cohorts (defined by year of treatment initiation) was also established.Results
The median number of patients per GP was 143 (IQR: 66–246). At the time of down-referral to private GPs, 13.8% of the patients had CD4 count <200 cell/mm3, this proportion reduced to 6.6% at 12 months and 4.1% at 48 months. Similarly, 88.4% of the patients had suppressed viral load (defined as HIV-1 RNA <400 copies/ml) at 48 months. The patients’ probability of survival at 12 and 48 months was 99.0% (95% CI: 98.4%–99.3%) and 89.0% (95% CI: 87.1%–90.0%) respectively. Patient retention at 48 months remained high at 94.3% (95% CI: 93.0%–95.7%).Conclusions
The study findings demonstrate the ability of the GPs to effectively maintain patient treatment outcomes and potentially contribute to HIV treatment scale-up with the relevant support mechanism. The model demonstrates how an assisted private sector based programme can be effectively and efficiently used to either target specific health concerns, key populations or serve as a stop-gap measure to meet urgent health needs. 相似文献168.
Shiby Kuriakose Helen M. Muleme Chukwunonso Onyilagha Rani Singh Ping Jia Jude E. Uzonna 《PloS one》2012,7(11)
Background
Trypanosoma congolense are extracellular and intravascular blood parasites that cause debilitating acute or chronic disease in cattle and other domestic animals. Diminazene aceturate (Berenil) has been widely used as a chemotherapeutic agent for trypanosomiasis in livestock since 1955. As in livestock, treatment of infected highly susceptible BALB/c mice with Berenil leads to rapid control of parasitemia and survival from an otherwise lethal infection. The molecular and biochemical mechanisms of action of Berenil are still not very well defined and its effect on the host immune system has remained relatively unstudied. Here, we investigated whether Berenil has, in addition to its trypanolytic effect, a modulatory effect on the host immune response to Trypanosoma congolense.Methodology/Principal Findings
BALB/c and C57BL/6 mice were infected intraperitoneally with T. congolense, treated with Berenil and the expression of CD25 and FoxP3 on splenic cells was assessed directly ex vivo. In addition, serum levels and spontaneous and LPS-induced production of pro-inflammatory cytokines by splenic and hepatic CD11b+ cells were determined by ELISA. Berenil treatment significantly reduced the percentages of CD25+ cells, a concomitant reduction in the percentage of regulatory (CD4+Foxp3+) T cells and a striking reduction in serum levels of disease exacerbating pro-inflammatory cytokines including IL-6, IL-12, TNF and IFN-γ. Furthermore, Berenil treatment significantly suppressed spontaneous and LPS-induced production of inflammatory cytokines by splenic and liver macrophages and significantly ameliorated LPS-induced septic shock and the associated cytokine storm.Conclusions/Significance
Collectively, these results provide evidence that in addition to its direct trypanolytic effect, Berenil also modulates the host immune response to the parasite in a manner that dampen excessive immune activation and production of pathology-promoting pro-inflammatory cytokines, suggesting that this drug may also be beneficial for treatment of disease conditions caused by excessive production of inflammatory cytokines. 相似文献169.
Adams D Altucci L Antonarakis SE Ballesteros J Beck S Bird A Bock C Boehm B Campo E Caricasole A Dahl F Dermitzakis ET Enver T Esteller M Estivill X Ferguson-Smith A Fitzgibbon J Flicek P Giehl C Graf T Grosveld F Guigo R Gut I Helin K Jarvius J Küppers R Lehrach H Lengauer T Lernmark Å Leslie D Loeffler M Macintyre E Mai A Martens JH Minucci S Ouwehand WH Pelicci PG Pendeville H Porse B Rakyan V Reik W Schrappe M Schübeler D Seifert M Siebert R Simmons D Soranzo N Spicuglia S Stratton M 《Nature biotechnology》2012,30(3):224-226
170.
Malaria is caused by Plasmodium species, whose transmission to vertebrate hosts is facilitated by mosquito vectors. The transition from the cold blooded
mosquito vector to the host represents physiological stress to the parasite, and additionally malaria blood stage infection
is characterised by intense fever periods. In recent years, it has become clear that heat shock proteins play an essential
role during the parasite's life cycle. Plasmodium falciparum expresses two prominent heat shock proteins: heat shock protein 70 (PfHsp70) and heat shock protein 90 (PfHsp90). Both of
these proteins have been implicated in the development and pathogenesis of malaria. In eukaryotes, Hsp70 and Hsp90 proteins
are functionally linked by an essential adaptor protein known as the Hsp70–Hsp90 organising protein (Hop). In this study,
recombinant P. falciparum Hop (PfHop) was heterologously produced in E. coli and purified by nickel affinity chromatography. Using specific anti-PfHop antisera, the expression and localisation of PfHop
in P. falciparum was investigated. PfHop was shown to co-localise with PfHsp70 and PfHsp90 in parasites at the trophozoite stage. Gel filtration
and co-immunoprecipitation experiments suggested that PfHop was present in a complex together with PfHsp70 and PfHsp90. The
association of PfHop with both PfHsp70 and PfHsp90 suggests that this protein may mediate the functional interaction between
the two chaperones. 相似文献