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61.
Schonn I Hennesen J Dartsch DC 《Apoptosis : an international journal on programmed cell death》2011,16(4):359-369
For DNA targeting anticancer drugs, cellular DNA repair mechanisms may cause resistance and hamper the therapeutic outcome.
DNA damage induced by topoisomerase IIα inhibitors like etoposide and anthracyclines, which are a mainstay of cancer therapy,
is also repaired in many cell types, but the impact and precise mechanisms of this repair are still obscure. To investigate
the DNA damage response of human adenocarcinoma HT29-cells to doxorubicin and to compare the involvement of Ku70 and Rad51
in the repair of doxorubicin- versus etoposide-induced DNA damage, we assessed cell cycle distribution and cell death, DNA
damage, proteins relevant for repair by homologous recombination and non-homologous end-joining, and clonogenicity following
exposure to doxorubicin at clinically achievable concentrations. Also, we assessed changes in the repair kinetics after siRNA-mediated
attenuation of Ku70 or Rad51 expression. We found that exposure to doxorubicin for 24 h induced a substantial amount of DNA
damage that was largely repaired when doxorubicin was removed and the cells were maintained in drug-free medium. Nevertheless,
a pronounced G2/M arrest occurred at times when repair was maximal. This was followed by a distinct increase in cell death and loss of clonogenicity.
In this regard, responses to doxorubicin and etoposide were similar. However, distinct differences in the repair process following
doxorubicin versus etoposide were seen in concentration dependency, time-course and requirement of Ku70 and Rad51 proteins.
In spite of the shared molecular target of doxorubicin and etoposide, DNA lesions induced by these compounds are repaired
differently. 相似文献
62.
Rose I Biuković G Aderhold P Müller V Grüber G Averhoff B 《Extremophiles : life under extreme conditions》2011,15(2):191-202
Thermus thermophilus is a model strain to unravel the molecular basis of horizontal gene transfer in hot environments. Previous genetic studies
led to the identification of a macromolecular transport machinery mediating DNA uptake in an energy-dependent manner. Here,
we have addressed how the transporter is energized. Inspection of the genome sequence revealed four putative transport (AAA)
ATPases but only the deletion of one, PilF, led to a transformation defect. PilF is similar to transport ATPases of type IV
and type II secretions systems but has a unique N-terminal sequence that carries a triplicated GSPII domain. To characterize
PilF biochemically it was produced in Escherichia coli and purified. The recombinant protein displayed NTPase activity with a preference for ATP. Gel filtration analyses combined
with dynamic light scattering demonstrated that PilF is monodispersed in solution and forms a complex of 590 ± 30 kDa, indicating
a homooligomer of six subunits. It contains a tetracysteine motif, previously shown to bind Zn2+ in related NTPases. Using atomic absorption spectroscopy, indeed Zn2+ was detected in the enzyme, but in contrast to all known zinc-binding traffic NTPases only one zinc atom was bound to the
hexamer. Deletion of the four cysteine residues led to a loss of Zn2+. Nevertheless, the mutant protein retained ATPase activity and hexameric complex formation. 相似文献
63.
64.
Cairns M Ghani A Okell L Gosling R Carneiro I Anto F Asoala V Owusu-Agyei S Greenwood B Chandramohan D Milligan P 《PloS one》2011,6(4):e18947
Background
Intermittent preventive treatment in infants (IPTi) with sulfadoxine-pyrimethamine (SP) is recommended by WHO where malaria incidence in infancy is high and SP resistance is low. The current delivery strategy is via routine Expanded Program on Immunisation contacts during infancy (EPI-IPTi). However, improvements to this approach may be possible where malaria transmission is seasonal, or where the malaria burden lies mainly outside infancy.Methods and Findings
A mathematical model was developed to estimate the protective efficacy (PE) of IPT against clinical malaria in children aged 2-24 months, using entomological and epidemiological data from an EPI-IPTi trial in Navrongo, Ghana to parameterise the model. The protection achieved by seasonally-targeted IPT in infants (sIPTi), seasonal IPT in children (sIPTc), and by case-management with long-acting artemisinin combination therapies (LA-ACTs) was predicted for Navrongo and for sites with different transmission intensity and seasonality. In Navrongo, the predicted PE of sIPTi was 26% by 24 months of age, compared to 16% with EPI-IPTi. sIPTc given to all children under 2 years would provide PE of 52% by 24 months of age. Seasonally-targeted IPT retained its advantages in a range of transmission patterns. Under certain circumstances, LA-ACTs for case-management may provide similar protection to EPI-IPTi. However, EPI-IPTi or sIPT combined with LA-ACTs would be substantially more protective than either strategy used alone.Conclusion
Delivery of IPT to infants via the EPI is sub-optimal because individuals are not protected by IPT at the time of highest malaria risk, and because older children are not protected. Alternative delivery strategies to the EPI are needed where transmission varies seasonally or the malaria burden extends beyond infancy. Long-acting ACTs may also make important reductions in malaria incidence. However, delivery systems must be developed to ensure that both forms of chemoprevention reach the individuals who are most exposed to malaria. 相似文献65.
Marta Lydka Ilona Kopera-Sobota Malgorzata Kotula-Balak Katarzyna Chojnacka Dorota Zak Barbara Bilinska 《Acta veterinaria Scandinavica》2011,53(1):12
Background
The dynamic cross-talk between epididymal cells is hormonally regulated and, in part, through direct cell-to-cell interactions. To date, no information is available regarding possible impact of anti-androgens on the proteins involved in the gap junctional communication within the boar epididymis. Thus, a question arised whether prenatal or postnatal exposure to an anti-androgen flutamide alters the expression of gap junction protein - connexin43 (Cx43) and androgen receptor (AR) expression in the caput, corpus and cauda epididymis and leads to delayed effects on morphology and function of adult pig epididymis. 相似文献66.
67.
Effect of S-methylmethionine on the photosynthesis in maize at different chilling temperatures 总被引:1,自引:0,他引:1
Eszter Kósa Dóra Szegő Eszter Horváth Ilona Rácz Zoltán Szigeti Demeter Lásztity Emil Páldi 《Central European Journal of Biology》2011,6(1):75-83
The effect of the natural compound S-methylmethionine (SMM) on the functioning of the photosynthetic apparatus, the efficiency
of photosynthesis and the synthesis of stress-induced phenoloids and anthocyanins involved in defence was investigated in
young maize plants exposed to moderate and severe chilling stress. Damage to PSII was observed as a reduction in the value
of variable fluorescence (Fv/Fm) which could be detected even after few hours of mild chilling stress. At temperatures below
10°C, the reduction in Fv/Fm was more pronounced. Changes in the value of net photosynthesis exhibited a similar tendency.
SMM has a moderating effect on this reduction and its protective effect was more pronounced under long-lasting chilling stress
and at the lowest temperatures. Monitoring of fluorescence intensities and ratios correlated with the levels of stress defence
compounds. The fluorescence intensities were found to increase over the course of chilling stress in response to SMM, with
the highest values being recorded in plants exposed to the longest period of stress. A similar tendency was observed for the
quantity of anthocyanins. The results confirm the complex role of SMM, which is manifested both in preserving the ability
of the photosynthetic apparatus to function and in stimulating the synthesis of metabolites involved in stress defence. 相似文献
68.
The development of cortical functions and the capacity of the mature brain to learn are largely determined by the establishment and maintenance of neocortical networks. Here we address the human development of long-range connectivity in primary visual and motor cortices, using well-established behavioral measures--a Contour Integration test and a Finger-tapping task--that have been shown to be related to these specific primary areas, and the long-range neural connectivity within those. Possible confounding factors, such as different task requirements (complexity, cognitive load) are eliminated by using these tasks in a learning paradigm. We find that there is a temporal lag between the developmental timing of primary sensory vs. motor areas with an advantage of visual development; we also confirm that human development is very slow in both cases, and that there is a retained capacity for practice induced plastic changes in adults. This pattern of results seems to point to human-specific development of the "canonical circuits" of primary sensory and motor cortices, probably reflecting the ecological requirements of human life. 相似文献
69.
Marta Narczyk Marta Ilona Wojty Ivana Le
i Aler Biserka
ini Marija Lui Elbieta Katarzyna Jagusztyn-Krynicka Zoran tefani Agnieszka Bzowska 《Journal of enzyme inhibition and medicinal chemistry》2022,37(1):1083
Helicobacter pylori represents a global health threat with around 50% of the world population infected. Due to the increasing number of antibiotic-resistant strains, new strategies for eradication of H. pylori are needed. In this study, we suggest purine nucleoside phosphorylase (PNP) as a possible new drug target, by characterising its interactions with 2- and/or 6-substituted purines as well as the effect of these compounds on bacterial growth. Inhibition constants are in the micromolar range, the lowest being that of 6-benzylthio-2-chloropurine. This compound also inhibits H. pylori 26695 growth at the lowest concentration. X-ray structures of the complexes of PNP with the investigated compounds allowed the identification of interactions of inhibitors in the enzyme’s base-binding site and the suggestion of structures that could bind to the enzyme more tightly. Our findings prove the potential of PNP inhibitors in the design of drugs against H. pylori. 相似文献
70.