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881.
Yuli Wu Manorama Tewari Shijun Cui Raphael Rubin 《Journal of cellular physiology》1996,168(3):499-509
The effect of insulin-like growth factor (IGF) on tumor necrosis factor (TNF)-induced cell killing was determined for mouse BALB/c3T3 fibroblasts in vitro. Cells maintained in 0.5% fetal bovine serum (FBS) were killed by TNF within 6 h in a concentration-dependent manner, an effect that was prevented by IGF-I. TNF-induced cytotoxicity of 3T3 cells that overexpress the human IGF-I receptor (p6 cells) was prevented by IGF-I alone in the absence of serum. TNF-induced cell death was associated with the morphologic features of apoptosis and the release of low-molecular-weight DNA, both of which were prevented by IGF-I. Neither epidermal growth factor (EGF) nor platelet-derived growth factor (PDGF) protected p6 cells from TNF-induced apoptosis. The specific protective action of the IGF-I receptor was demonstrated further by the marked sensitivity to TNF of embryo fibroblasts derived from mice with targeted disruption of the IGF-I receptor (R cells) but not of fibroblasts derived from wild-type littermates or R cells transfected with the cDNA for the human IGF-I receptor. Cycloheximide or actinomycin D markedly reduced the protection offered by IGF-I. IGF-I protection of BALB/c3T3 cells persisted for up to 5 days in the presence of PDGF and EGF, whereas IGF-I lost its effectiveness after 2 days in the absence of growth factors. IGF-I did not prevent TNF-induced release of arachidonic acid. The results demonstrate a specific role for the IGF-I receptor in the protection against TNF cytotoxicity. This action of the IGF-I receptor is mediated by protective cytosolic proteins that exhibit a high rate of turnover and whose levels are regulated principally by factors within serum other than IGF-I. © 1996 Wiley-Liss, Inc. 相似文献
882.
The mechanism of EcoRI endonuclease is substrate dependent. At 37 degrees dissociation of the enzyme-Form II DNA intermediates of ColE1 DNA and bacteriophage G4 RFI DNA is negligible. Therefore, both DNA strands with in the EcoRI sequence are cleaved during a single binding event. However, double strand cleavage of SV40 DNA occurs without dissociation of the enzyme in only 75% of the catalytic events. This mechanistic difference presumably reflects sequence differences about the EcoRI sites of these DNA's. 相似文献
883.
884.
Kenyon GL DeMarini DM Fuchs E Galas DJ Kirsch JF Leyh TS Moos WH Petsko GA Ringe D Rubin GM Sheahan LC;National Research Council Steering Committee 《Molecular & cellular proteomics : MCP》2002,1(10):763-780
Research in proteomics is the next step after genomics in understanding life processes at the molecular level. In the largest sense proteomics encompasses knowledge of the structure, function and expression of all proteins in the biochemical or biological contexts of all organisms. Since that is an impossible goal to achieve, at least in our lifetimes, it is appropriate to set more realistic, achievable goals for the field. Up to now, primarily for reasons of feasibility, scientists have tended to concentrate on accumulating information about the nature of proteins and their absolute and relative levels of expression in cells (the primary tools for this have been 2D gel electrophoresis and mass spectrometry). Although these data have been useful and will continue to be so, the information inherent in the broader definition of proteomics must also be obtained if the true promise of the growing field is to be realized. Acquiring this knowledge is the challenge for researchers in proteomics and the means to support these endeavors need to be provided. An attempt has been made to present the major issues confronting the field of proteomics and two clear messages come through in this report. The first is that the mandate of proteomics is and should be much broader than is frequently recognized. The second is that proteomics is much more complicated than sequencing genomes. This will require new technologies but it is highly likely that many of these will be developed. Looking back 10 to 20 years from now, the question is: Will we have done the job wisely or wastefully? This report summarizes the presentations made at a symposium at the National Academy of Sciences on February 25, 2002. 相似文献
885.
Leng-Chu Shi Hoau-Yan Wang Joel Horwitz Eitan Friedman 《Journal of neurochemistry》1996,67(4):1478-1484
Abstract: Platelet-activating factor (PAF) may be a neuromodulator involved in neural cell differentiation, cerebral inflammation, and ischemia. The PAF receptor is a member of the G protein-coupled receptor superfamily. In the present study, we sought to define the specific G protein(s) that mediate PAF-stimulated phosphoinositide (PI) metabolism in an immortalized hippocampal cell line, HN33.11. PAF increased the production of 3 H-labeled inositol phosphates (IPs) with EC50 values of 1.2–1.5 n M . The effect of PAF on 3 H-IPs formation was completely blocked by the PAF antagonist BN 50739 at a concentration of 300 n M . Pertussis toxin pretreatment attenuated PAF-stimulated 3 H-IPs production by 20–30% ( p < 0.05). Consistent with a role for Gi1/2 in this response, antiserum against Gαi1/2 blocked the response to a similar degree. Pretreatment of permeabilized cells with Gαq/11 antiserum attenuated the response by 70% ( p < 0.05), suggesting a role for Gq/11 in mediating the PAF response in this cell line. Stimulation with PAF increased [α-32 P]-GTP binding to both Gαq and Gαi1/2 proteins. Moreover, specific [3 H]PAF binding sites coprecipitated with Gαq and Gαi1/2 proteins. The results suggest that PAF-stimulated PI metabolism in HN33.11 cells is mediated by both Gq and Gi1/2 proteins. 相似文献
886.
Annotation of the Drosophila melanogaster euchromatic genome: a systematic review 总被引:1,自引:0,他引:1 下载免费PDF全文
Misra S Crosby MA Mungall CJ Matthews BB Campbell KS Hradecky P Huang Y Kaminker JS Millburn GH Prochnik SE Smith CD Tupy JL Whitfied EJ Bayraktaroglu L Berman BP Bettencourt BR Celniker SE de Grey AD Drysdale RA Harris NL Richter J Russo S Schroeder AJ Shu SQ Stapleton M Yamada C Ashburner M Gelbart WM Rubin GM Lewis SE 《Genome biology》2002,3(12):research0083.1-8322
887.
Rel(Mtb) of Mycobacterium tuberculosis is responsible for the intracellular regulation of (p)ppGpp and the consequent ability of the organism to survive long-term starvation, indicating a possible role in the pathogenesis of tuberculosis. Purified Rel(Mtb) is a dual-function enzyme carrying out ATP: GTP/GDP/ITP 3'-pyrophosphoryltransferase and (p)ppGpp 3'-pyrophosphohydrolase reactions. Here we show that in the absence of biological regulators, Rel(Mtb) simultaneously catalyzes both transferase and hydrolysis at the maximal rate for each reaction, indicating the existence of two distinct active sites. The differential regulation of the opposing activities of Rel(Mtb) is dependent on the ratio of uncharged to charged tRNA and the association of Rel(Mtb) with a complex containing tRNA, ribosomes, and mRNA. A 20-fold increase in the k(cat) and a 4-fold decrease in K(ATP) and K(GTP) from basal levels for transferase activity occur when Rel(Mtb) binds to a complex containing uncharged tRNA, ribosomes, and mRNA (Rel(Mtb) activating complex or RAC). The k(cat) for hydrolysis, however, is reduced 2-fold and K(m) for pppGpp increased 2-fold from basal levels in the presence of the Rel(Mtb) activating complex. The addition of charged tRNA to this complex has the opposite effect by inhibiting transferase activity and activating hydrolysis activity. Differential control of Rel(Mtb) gives the Mtb ribosomal complex a new regulatory role in controlling cellular metabolism in response to stringent growth conditions that may be present in the dormant Mtb lesion. 相似文献
888.
James B Adams Matthew Baral Elizabeth Geis Jessica Mitchell Julie Ingram Andrea Hensley Irene Zappia Sanford Newmark Eva Gehn Robert A Rubin Ken Mitchell Jeff Bradstreet Jane El-Dahr 《BMC clinical pharmacology》2009,9(1):1-22
Background
This study investigated the effect of oral dimercapto succinic acid (DMSA) therapy for children with autism spectrum disorders ages 3-8 years.Methods
Phase 1 involved 65 children who received one round of DMSA (3 days). Participants who had high urinary excretion of toxic metals were selected to continue on to phase 2. In phase 2, 49 participants were randomly assigned in a double-blind design to receive an additional 6 rounds of either DMSA or placebo.Results
DMSA greatly increased the excretion of lead, substantially increased excretion of tin and bismuth, and somewhat increased the excretion of thallium, mercury, antimony, and tungsten. There was some increase in urinary excretion of essential minerals, especially potassium and chromium. The Phase 1 single round of DMSA led to a dramatic normalization of RBC glutathione in almost all cases, and greatly improved abnormal platelet counts, suggesting a significant decrease in inflammation.Conclusion
Overall, DMSA therapy seems to be reasonably safe, effective in removing several toxic metals (especially lead), dramatically effective in normalizing RBC glutathione, and effective in normalizing platelet counts. Only 1 round (3 days) was sufficient to improve glutathione and platelets. Additional rounds increased excretion of toxic metals. 相似文献889.
G. James Rubin Lena Hillert Rosa Nieto‐Hernandez Eric van Rongen Gunnhild Oftedal 《Bioelectromagnetics》2011,32(8):593-609
Idiopathic environmental intolerance attributed to electromagnetic fields (IEI‐EMF) is a controversial illness in which people report symptoms that they believe are triggered by exposure to EMF. Double‐blind experiments have found no association between the presence of EMF and self‐reported outcomes in people with IEI‐EMF. No systematic review has assessed whether EMF exposure triggers physiological or cognitive changes in this group. Using a systematic literature search, we identified 29 single or double‐blind experiments in which participants with IEI‐EMF were exposed to different EMF levels and in which objectively measured outcomes were assessed. Five studies identified significant effects of exposure such as reduced heart rate and blood pressure, altered pupillary light reflex, reduced visual attention and perception, improved spatial memory, movement away from an EMF source during sleep and altered EEG during sleep. In most cases, these were isolated results that other studies failed to replicate. For the sleep EEG findings, the results reflected similar changes in the IEI‐EMF participants and a non‐IEI‐EMF control group. At present, there is no reliable evidence to suggest that people with IEI‐EMF experience unusual physiological reactions as a result of exposure to EMF. This supports suggestions that EMF is not the main cause of their ill health. Bioelectromagnetics. Bioelectromagnetics 32:593–609, 2011. © 2011 Wiley Periodicals, Inc. 相似文献
890.
Sheng-Jian Li Ten-Yang Yen Yoshimi Endo Malgorzata Klauzinska Bolormaa Baljinnyam Bruce Macher Robert Callahan Jeffrey S. Rubin 《Cellular signalling》2009,21(6):916-925
R-spondins (Rspos) potentiate Wnt/β-catenin signaling, an important pathway in embryonic development that is constitutively active in many cancers. To analyze Rspo structure and function, we expressed full-length wild-type Rspo2 and Rspo2 point mutants corresponding to Rspo4 variants that have been linked to developmental defects. The Rspo2 mutants had markedly reduced potency relative to the wild-type protein, demonstrating for the first time specific amino acid residues in Rspos that are critical for β-catenin signaling. The diminished activity of Rspo2/C78Y and Rspo2/C113R was attributable to a defect in their secretion, while Rspo2/Q70R exhibited a decrease in its intrinsic activity. Cysteine assignments in a Rspo2 derivative containing only the two furin-like domains (Rspo2-2F) provided the first information about the disulfide-bonding pattern of this motif, which was characterized by multiple short loops and unpaired cysteine residues, and established that the loss-of-function cysteine mutants disrupted disulfide bond formation. Moreover, Rspo2-2F demonstrated potent activity and synergized strongly with Wnt-3a in a β-catenin reporter assay. In contrast, an Rspo2-2F derivative containing the Q70R substitution showed significantly reduced activity, although it still synergized with Wnt-3a in the reporter assay. Rspo2-2F derivatives elicited an unusually sustained phosphorylation (20 h) of the Wnt co-receptor, low density lipoprotein receptor-related protein 6 (LRP6), as well as an increase in cell surface LRP6. Co-immunoprecipitation experiments involving LRP6 and Kremens suggested that these associations contribute to Rspo2 activity, although the lack of major differences between wild-type and Q70R derivatives implied that additional interactions may be important. 相似文献