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51.
Yoshikawa D Kopacek J Yamaguchi N Ishibashi D Yamanaka H Yamaguchi Y Katamine S Sakaguchi S 《Gene》2007,386(1-2):139-146
We and others previously showed that, in some lines of prion protein (PrP)-knockout mice, the downstream PrP-like protein (PrPLP/Dpl) was abnormally expressed in brains partly due to impaired cleavage/polyadenylation of the residual PrP promoter-driven pre-mRNA despite the presence of a poly(A) signal. In this study, we newly established an in vitro transient transfection system in which abnormal expression of PrPLP/Dpl can be visualized by expression of the green fluorescence protein, EGFP, in cultured cells. No EGFP was detected in cells transfected by a vector carrying a PrP genomic fragment including the region targeted in the knockout mice intact upstream of the PrPLP/Dpl gene. In contrast, deletion of the targeted region from the vector caused expression of EGFP. By employing this system with other vectors carrying various deletions or point mutations in the targeted region, we identified that disruption of the splicing elements in the PrP terminal intron caused the expression of EGFP. Recent lines of evidence indicate that terminal intron splicing and cleavage/polyadenylation of pre-mRNA are functionally linked to each other. Taken together, our newly established system shows that the abnormal expression of PrPLP/Dpl in PrP-knockout mice caused by the impaired cleavage/polyadenylation of the PrP promoter-driven pre-mRNA is due to the functional dissociation between the pre-mRNA machineries, in particular those of cleavage/polyadenylation and splicing. Our newly established in vitro system, in which the functional dissociation between the pre-mRNA machineries can be visualized by EGFP green fluorescence, may be useful for studies of the functional connection of pre-mRNA machineries. 相似文献
52.
Youhei Tanaka Naohiro Hayashibara Tomoya Enokido Makoto Takizawa 《Cluster computing》2007,10(1):81-93
In this paper, we discuss how to realize fault-tolerant applications on distributed objects. Servers supporting objects can
be fault-tolerant by taking advantage of replication and checkpointing technologies. However, there is no discussion on how
application programs being performed on clients are tolerant of clients faults. For example, servers might block in the two-phase
commitment protocol due to the client fault. We newly discuss how to make application programs fault-tolerant by taking advantage
of mobile agent technologies where a program can move from a computer to another computer in networks. An application program
to be performed on a faulty computer can be performed on another operational computer by moving the program in the mobile
agent model. In this paper, we discuss a transactional agent model where a reliable and efficient application for manipulating objects in multiple computers is realized in the mobile agent
model. In the transactional agent model, only a small part of the application program named routing subagent moves around computers. A routing subagent autonomously finds a computer which to visit next. We discuss a hierarchical navigation
map which computer should be visited price to another computer in a transactional agent. A routing subagent makes a decision
on which computer visit for the hierarchical navigation map. Programs manipulating objects in a computer are loaded to the
computer on arrival of the routing subagent in order to reduce the communication overhead. This part of the transactional
agent is a manipulating subagent. The manipulation subagent still exists on the computer even after the routing subagent leaves the computer in order to hold
objects until the commitment. We assume every computer may stop by fault while networks are reliable. There are kinds of faulty
computers for a transactional agent; current, destination, and sibling computers where a transactional agent now exists, will move, and has visited, respectively. The types of faults are detected
by neighbouring manipulation subagents by communicating with each other. If some of the manipulation subagents are faulty,
the routing subagent has to be aborted. However, the routing subagent is still moving. We discuss how to efficiently deliver
the abort message to the moving routing subagent. We evaluate the transactional agent model in terms of how long it takes
to abort the routing subagent if some computer is faulty.
相似文献
Makoto TakizawaEmail: |
53.
54.
The temperature‐dependent photoluminescences of Y2O3:Eu (6% Eu), Y2O3:Tb (4% Tb) and Y2O3:Tm (1% Tm) were investigated for high‐temperature phosphor thermometry. Two different phases, the monoclinic phase and cubic phase, were considered because the fluorescence spectra vary with the phase. To employ the intensity ratio method, we investigated their photoluminescence spectra under the excitation light of an Hg–Xe lamp as the temperature was elevated from room temperature to more than 1200 K. As a result, it was confirmed that the luminescence intensity of all of the phosphors varied with elevating temperature, i.e. thermal quenching, with the variations depending on the type of rare earth impurity and their phases. The results indicate that Y2O3:Eu phosphors are applicable to the intensity ratio method because they show appropriate variations in the intensity ratio of two emission lines, and they also have strong and sharp peak intensities without excessive optical noise or black body radiation over a wide range of temperatures. The intensity ratios for Y2O3:Tb provide such small variations with temperature that the temperature resolution is low, despite the strong emission intensities. As for Y2O3:Tm, the intensity ratios also have a low temperature resolution and their emission intensities are weak. Therefore, Y2O3:Tb and Y2O3:Tm are not appropriate for the intensity ratio method for phosphor thermometry. Copyright © 2010 John Wiley & Sons, Ltd. 相似文献
55.
Atarashi R Satoh K Sano K Fuse T Yamaguchi N Ishibashi D Matsubara T Nakagaki T Yamanaka H Shirabe S Yamada M Mizusawa H Kitamoto T Klug G McGlade A Collins SJ Nishida N 《Nature medicine》2011,17(2):175-178
The development of technologies for the in vitro amplification of abnormal conformations of prion protein (PrP(Sc)) has generated the potential for sensitive detection of prions. Here we developed a new PrP(Sc) amplification assay, called real-time quaking-induced conversion (RT-QUIC), which allows the detection of ≥1 fg of PrP(Sc) in diluted Creutzfeldt-Jakob disease (CJD) brain homogenate. Moreover, we assessed the technique first in a series of Japanese subjects and then in a blind study of 30 cerebrospinal fluid specimens from Australia, which achieved greater than 80% sensitivity and 100% specificity. These findings indicate the promising enhanced diagnostic capacity of RT-QUIC in the antemortem evaluation of suspected CJD. 相似文献
56.
Induction of cytoplasmic rods and rings structures by inhibition of the CTP and GTP synthetic pathway in mammalian cells 总被引:1,自引:0,他引:1
Carcamo WC Satoh M Kasahara H Terada N Hamazaki T Chan JY Yao B Tamayo S Covini G von Mühlen CA Chan EK 《PloS one》2011,6(12):e29690
Background
Cytoplasmic filamentous rods and rings (RR) structures were identified using human autoantibodies as probes. In the present study, the formation of these conserved structures in mammalian cells and functions linked to these structures were examined.Methodology/Principal Findings
Distinct cytoplasmic rods (∼3–10 µm in length) and rings (∼2–5 µm in diameter) in HEp-2 cells were initially observed in immunofluorescence using human autoantibodies. Co-localization studies revealed that, although RR had filament-like features, they were not enriched in actin, tubulin, or vimentin, and not associated with centrosomes or other known cytoplasmic structures. Further independent studies revealed that two key enzymes in the nucleotide synthetic pathway cytidine triphosphate synthase 1 (CTPS1) and inosine monophosphate dehydrogenase 2 (IMPDH2) were highly enriched in RR. CTPS1 enzyme inhibitors 6-diazo-5-oxo-L-norleucine and Acivicin as well as the IMPDH2 inhibitor Ribavirin exhibited dose-dependent induction of RR in >95% of cells in all cancer cell lines tested as well as mouse primary cells. RR formation by lower concentration of Ribavirin was enhanced in IMPDH2-knockdown HeLa cells whereas it was inhibited in GFP-IMPDH2 overexpressed HeLa cells. Interestingly, RR were detected readily in untreated mouse embryonic stem cells (>95%); upon retinoic acid differentiation, RR disassembled in these cells but reformed when treated with Acivicin.Conclusions/Significance
RR formation represented response to disturbances in the CTP or GTP synthetic pathways in cancer cell lines and mouse primary cells and RR are the convergence physical structures in these pathways. The availability of specific markers for these conserved structures and the ability to induce formation in vitro will allow further investigations in structure and function of RR in many biological systems in health and diseases. 相似文献57.
Suzuki H Ikeda N Kobayashi K Terashima Y Shimada Y Suzuki T Hagiwara T Hatakeyama S Nagaoka K Yoshida J Saito Y Tanaka J Hayashi M 《Mutation research》2005,583(2):133-145
We conducted simultaneous liver and peripheral blood micronucleus assays in young rats with seven rodent hepatocarcinogens-4,4'-methylenedianiline (MDA), quinoline, o-toluidine, 4-chloro-o-phenylenediamine (CPDA), dimethylnitrosamine (DMN), p-dimethylaminoazobenzene (DAB), and di(2-ethylhexyl)phthalate (DEHP)-and two mutagenic chemicals-kojic acid and methylmethanesulfonate (MMS). Quinoline, DMN, and DAB were positive in the liver assay, while o-toluidine, kojic acid, DAB, and MMS were positive in the peripheral blood assay. o-Toluidine, kojic acid, and DAB are reportedly negative in mouse bone marrow micronucleus assays, indicating a species difference. Our results revealed a correlation between micronucleus induction in hepatocytes and hepatocarcinogenicity. This technique can be useful for the detection of micronucleus-inducing chemicals that require metabolic activation, and it enables simultaneous comparison of the micronucleus-inducing potential of chemicals in the liver and peripheral blood in the same individual. 相似文献
58.
Naohiro?Yoshimoto Toru?SatoEmail author Yutaka?Kondo 《Journal of applied phycology》2005,17(3):207-214
For a photobioreactor for mass-culturing microalgae, it is known that flashing light effect enhances the efficiency of photosynthesis. A dynamic model for photosynthesis was developed to elucidate this effect. A particular feature of the model is that discrete RuBP particles circulate in the Calvin cycle and their speeds in the cycle are determined by the amount of ATP generated in the photon reception process. This can realise the light saturation under continuous light and the flashing light effect under fluctuating illumination. Laboratory experiments were conducted to obtain model parameters by curve-fitting for Chaetoceros calcitrans. The present model demonstrates the light flashing effect moderately well and elucidates its mechanism reasonably. 相似文献
59.
ASC-mediated NF-kappaB activation leading to interleukin-8 production requires caspase-8 and is inhibited by CLARP 总被引:3,自引:0,他引:3
Hasegawa M Imamura R Kinoshita T Matsumoto N Masumoto J Inohara N Suda T 《The Journal of biological chemistry》2005,280(15):15122-15130
ASC is an adaptor molecule that mediates apoptotic and inflammatory signals from several Apaf-1-like molecules, including CARD12/Ipaf, cryopyrin/PYPAF1, PYPAF5, PYPAF7, and NALP1. To characterize the signaling pathway mediated by ASC, we established cell lines in which muramyl dipeptide, the bacterial component recognized by another Apaf-1-like molecule, Nod2, induced an interaction between a CARD12-Nod2 chimeric protein and ASC, and elicited cell autonomous NF-kappaB activation. This response required caspase-8, and was suppressed by CLARP/FLIP, an inhibitor of caspase-8. The catalytic activity of caspase-8 was required for the ASC-mediated NF-kappaB activation when caspase-8 was expressed at an endogenous level, although it was not essential when caspase-8 was overexpressed. In contrast, FADD, the adaptor protein linking Fas and caspase-8, was not required for this response. Consistently, ASC recruited caspase-8 and CLARP but not FADD and Nod2 to its speck-like aggregates in cells. Finally, muramyl dipeptide induced interleukin-8 production in MAIL8 cells. These results are the first to indicate that caspase-8 plays an important role in the ASC-mediated NF-kappaB activation, and that the ASC-mediated NF-kappaB activation actually induces physiologically relevant gene expression. 相似文献
60.