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101.
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103.
Jérémie Gautheron Gilles Courtois 《Cellular and molecular life sciences : CMLS》2010,67(18):3101-3113
Ubiquitination has emerged over the years as the most sophisticated way to modify proteins to affect their fate and function.
In particular, it has been reported to be instrumental in regulating several steps of the NF-κB signalling pathway which controls
inflammation, immunity, adhesion and cell survival. Integrating ubiquitination into NF-κB activation requires the regulatory
subunit of IKK, NEMO, which not only displays affinity for polyubiquitin chains, but is also posttranslationally modified
by a complex set of reactions involving ubiquitin. Here, we examine how studies of the NEMO/ubiquitin relationship have provided
novel insights into the IKK activation process and have uncovered molecular mechanisms that should represent in the future
attractive targets for specifically modulating NF-κB function. 相似文献
104.
Karen Schrader Jisen Huai Lars Jöckel Carolin Oberle Christoph Borner 《Cellular and molecular life sciences : CMLS》2010,67(10):1607-1618
Caspases are the most important effectors of apoptosis, the major form of programmed cell death (PCD) in multicellular organisms. This is best reflected by the appearance of serious development defects in mice deficient for caspase-8, -9, and -3. Meanwhile, caspase-independent PCD, mediated by other proteases or signaling components has been described in numerous publications. Although we do not doubt that such cell death exists, we propose that it has evolved later during evolution and is most likely not designed to execute, but to amplify and speed-up caspase-dependent cell death. This review shall provide evidence for such a concept. 相似文献
105.
Bernd Kaina Geoffrey P. Margison Markus Christmann 《Cellular and molecular life sciences : CMLS》2010,67(21):3663-3681
O
6-methylguanine-DNA methyltransferase (MGMT) repairs the cancer chemotherapy-relevant DNA adducts, O
6-methylguanine and O
6-chloroethylguanine, induced by methylating and chloroethylating anticancer drugs, respectively. These adducts are cytotoxic,
and given the overwhelming evidence that MGMT is a key factor in resistance, strategies for inactivating MGMT have been pursued.
A number of drugs have been shown to inactivate MGMT in cells, human tumour models and cancer patients, and O
6-benzylguanine and O
6-[4-bromothenyl]guanine have been used in clinical trials. While these agents show no side effects per se, they also inactivate
MGMT in normal tissues and hence exacerbate the toxic side effects of the alkylating drugs, requiring dose reduction. This
might explain why, in any of the reported trials, the outcome has not been improved by their inclusion. It is, however, anticipated
that, with the availability of tumour targeting strategies and hematopoetic stem cell protection, MGMT inactivators hold promise
for enhancing the effectiveness of alkylating agent chemotherapy. 相似文献
106.
Roscioli T Kamsteeg EJ Buysse K Maystadt I van Reeuwijk J van den Elzen C van Beusekom E Riemersma M Pfundt R Vissers LE Schraders M Altunoglu U Buckley MF Brunner HG Grisart B Zhou H Veltman JA Gilissen C Mancini GM Delrée P Willemsen MA Ramadža DP Chitayat D Bennett C Sheridan E Peeters EA Tan-Sindhunata GM de Die-Smulders CE Devriendt K Kayserili H El-Hashash OA Stemple DL Lefeber DJ Lin YY van Bokhoven H 《Nature genetics》2012,44(5):581-585
Walker-Warburg syndrome (WWS) is an autosomal recessive multisystem disorder characterized by complex eye and brain abnormalities with congenital muscular dystrophy (CMD) and aberrant a-dystroglycan glycosylation. Here we report mutations in the ISPD gene (encoding isoprenoid synthase domain containing) as the second most common cause of WWS. Bacterial IspD is a nucleotidyl transferase belonging to a large glycosyltransferase family, but the role of the orthologous protein in chordates is obscure to date, as this phylum does not have the corresponding non-mevalonate isoprenoid biosynthesis pathway. Knockdown of ispd in zebrafish recapitulates the human WWS phenotype with hydrocephalus, reduced eye size, muscle degeneration and hypoglycosylated a-dystroglycan. These results implicate ISPD in a-dystroglycan glycosylation in maintaining sarcolemma integrity in vertebrates. 相似文献
107.
108.
Bolin C Boudra MT Fernet M Vaslin L Pennaneach V Zaremba T Biard D Cordelières FP Favaudon V Mégnin-Chanet F Hall J 《Cellular and molecular life sciences : CMLS》2012,69(6):951-962
Cyclin-dependent kinase 5 (Cdk5) has been identified as a determinant of sensitivity to poly(ADP-ribose) polymerase (PARP) inhibitors. Here, the consequences of its depletion on cell survival, PARP activity, the recruitment of base excision repair (BER) proteins to DNA damage sites, and overall DNA single-strand break (SSB) repair were investigated using isogenic HeLa stably depleted (KD) and Control cell lines. Synthetic lethality achieved by disrupting PARP activity in Cdk5-deficient cells was confirmed, and the Cdk5KD cells were also found to be sensitive to the killing effects of ionizing radiation (IR) but not methyl methanesulfonate or neocarzinostatin. The recruitment profiles of GFP-PARP-1 and XRCC1-YFP to sites of micro-irradiated Cdk5KD cells were slower and reached lower maximum values, while the profile of GFP-PCNA recruitment was faster and attained higher maximum values compared to Control cells. Higher basal, IR, and hydrogen peroxide-induced polymer levels were observed in Cdk5KD compared to Control cells. Recruitment of GFP-PARP-1 in which serines 782, 785, and 786, potential Cdk5 phosphorylation targets, were mutated to alanines in micro-irradiated Control cells was also reduced. We hypothesize that Cdk5-dependent PARP-1 phosphorylation on one or more of these serines results in an attenuation of its ribosylating activity facilitating persistence at DNA damage sites. Despite these deficiencies, Cdk5KD cells are able to effectively repair SSBs probably via the long patch BER pathway, suggesting that the enhanced radiation sensitivity of Cdk5KD cells is due to a role of Cdk5 in other pathways or the altered polymer levels. 相似文献
109.
Eugene Kouassi Joel Sango J.M. Bosson Brou Francis N. Teubissi Kern O. Kymn 《Journal of forecasting》2012,31(7):617-638
In this paper we extend the works of Baillie and Baltagi (1999, in Analysis of Panels and Limited Dependent Variables Models, Hsiao C et al. (eds). Cambridge University Press: Cambridge, UK; 255–267) and generalize certain results from the Baltagi and Li (1992, Journal of Forecasting 11 : 561–567) paper accounting for AR(1) errors in the disturbance term. In particular, we derive six predictors for the one‐way error components model, as well as their associated asymptotic mean squared error of multi‐step prediction in the presence of AR(1) errors in the disturbance term. In addition, we also provide both theoretical and simulation evidence as to the relative efficiency of our alternative predictors. The adequacy of the prediction AMSE formula is also investigated by the use of Monte Carlo methods and indicates that the ordinary optimal predictor performs well for various accuracy criteria. Copyright © 2011 John Wiley & Sons, Ltd. 相似文献
110.