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231.
The mitochondrial gateway to cell death is a frequent target for tumor suppressors, which largely utilize Bcl-2-dependent apoptotic pathways. Reporting in Science, Giorgi et al. (2010) now show that PML exerts its tumor suppressor function via a distinct mechanism: Ca2(+) transfer from the endoplasmic reticulum to the mitochondria. 相似文献
232.
Structural and Functional Analysis of Viral siRNAs 总被引:1,自引:0,他引:1
Gyorgy Szittya Simon Moxon Vitantonio Pantaleo Gabor Toth Rachel L. Rusholme Pilcher Vincent Moulton Jozsef Burgyan Tamas Dalmay 《PLoS pathogens》2010,6(4)
A large amount of short interfering RNA (vsiRNA) is generated from plant viruses during infection, but the function, structure and biogenesis of these is not understood. We profiled vsiRNAs using two different high-throughput sequencing platforms and also developed a hybridisation based array approach. The profiles obtained through the Solexa platform and by hybridisation were very similar to each other but different from the 454 profile. Both deep sequencing techniques revealed a strong bias in vsiRNAs for the positive strand of the virus and identified regions on the viral genome that produced vsiRNA in much higher abundance than other regions. The hybridisation approach also showed that the position of highly abundant vsiRNAs was the same in different plant species and in the absence of RDR6. We used the Terminator 5′-Phosphate-Dependent Exonuclease to study the 5′ end of vsiRNAs and showed that a perfect control duplex was not digested by the enzyme without denaturation and that the efficiency of the Terminator was strongly affected by the concentration of the substrate. We found that most vsiRNAs have 5′ monophosphates, which was also confirmed by profiling short RNA libraries following either direct ligation of adapters to the 5′ end of short RNAs or after replacing any potential 5′ ends with monophosphates. The Terminator experiments also showed that vsiRNAs were not perfect duplexes. Using a sensor construct we also found that regions from the viral genome that were complementary to non-abundant vsiRNAs were targeted in planta just as efficiently as regions recognised by abundant vsiRNAs. Different high-throughput sequencing techniques have different reproducible sequence bias and generate different profiles of short RNAs. The Terminator exonuclease does not process double stranded RNA, and because short RNAs can quickly re-anneal at high concentration, this assay can be misleading if the substrate is not denatured and not analysed in a dilution series. The sequence profiles and Terminator digests suggest that CymRSV siRNAs are produced from the structured positive strand rather than from perfect double stranded RNA or by RNA dependent RNA polymerase. 相似文献
233.
Frank Gibson Christine Hoogland Salvador Martinez‐Bartolomé J. Alberto Medina‐Aunon Juan Pablo Albar Gyorgy Babnigg Anil Wipat Henning Hermjakob Jonas S. Almeida Romesh Stanislaus Norman W. Paton Andrew R. Jones 《Proteomics》2010,10(17):3073-3081
The Human Proteome Organisation's Proteomics Standards Initiative has developed the GelML (gel electrophoresis markup language) data exchange format for representing gel electrophoresis experiments performed in proteomics investigations. The format closely follows the reporting guidelines for gel electrophoresis, which are part of the Minimum Information About a Proteomics Experiment (MIAPE) set of modules. GelML supports the capture of metadata (such as experimental protocols) and data (such as gel images) resulting from gel electrophoresis so that laboratories can be compliant with the MIAPE Gel Electrophoresis guidelines, while allowing such data sets to be exchanged or downloaded from public repositories. The format is sufficiently flexible to capture data from a broad range of experimental processes, and complements other PSI formats for MS data and the results of protein and peptide identifications to capture entire gel‐based proteome workflows. GelML has resulted from the open standardisation process of PSI consisting of both public consultation and anonymous review of the specifications. 相似文献
234.
Gunduz O Sipos F Spagnolo B Kocsis L Magyar A Orosz G Borsodi A Calò G Benyhe S 《Neuro-Signals》2006,15(2):91-101
Following the discovery of nociceptin/orphanin FQ (N/OFQ) peptide receptor (NOP) and its endogenous ligand, an extensive search has started to find selective agonists and antagonists targeting this novel receptor-ligand system due to their therapeutic potentials. By the help of the combinatorial chemistry a series of hexapeptides with a general formula of Ac-RYY-R/K-W/I-R/K-NH(2) having high NOP receptor affinity and selectivity were identified. On the basis of this information we developed a number of novel compounds. The detailed structure-activity studies on the partial agonist Ac-RYYRIK-NH(2) are reported in this communication. Besides the modifications on N- and C-terminal, Arg-Cit exchange was performed on the template structure. The novel hexapeptides were analyzed in radioligand binding, functional biochemical [(35)S]GTPgammaS binding assays by using membranes from rat brains and Chinese hamster ovary cells expressing human NOP receptor. The agonist/antagonist properties were also tested on in the mouse vas deferens bioassay. C-terminal modification yielded a high affinity, selective and potent NOP ligand (Ac-RYYRIK-ol) with a partial agonist property. Several analogs of this compound were synthesized. The presence of the positively charged arginine residue at the first position turned out to be crucial for the biological activity of the hexapeptide. The N-terminal modifications with various acyl groups (ClAc, pivaloyl, formyl, benzoyl, mesyl) decreased the affinity of the ligand towards the receptor and the intrinsic activity for stimulating the G-protein activation was also decreased. The structure-activity studies on the hexapeptide derivatives provided some basic information on the structural requirements for receptor binding and activation. 相似文献
235.
This study addresses the energetic coupling between the activation and slow inactivation gates of Shaker potassium channels. To track the status of the activation gate in inactivated channels that are nonconducting, we used two functional assays: the accessibility of a cysteine residue engineered into the protein lining the pore cavity (V474C) and the liberation by depolarization of a Cs(+) ion trapped behind the closed activation gate. We determined that the rate of activation gate movement depends on the state of the inactivation gate. A closed inactivation gate favors faster opening and slower closing of the activation gate. We also show that hyperpolarization closes the activation gate long before a channel recovers from inactivation. Because activation and slow inactivation are ubiquitous gating processes in potassium channels, the cross talk between them is likely to be a fundamental factor in controlling ion flux across membranes. 相似文献
236.
Functional domains of histone deacetylase-3. 总被引:9,自引:0,他引:9
Wen-Ming Yang Shih-Chang Tsai Yu-Der Wen Gyorgy Fejer Edward Seto 《The Journal of biological chemistry》2002,277(11):9447-9454
237.
Yuefan Wang Tung-Shing Mamie Lih Naseruddin Höti Lori J. Sokoll Gregory Chesnut Gyorgy Petrovics Indu Kohaar Hui Zhang 《Proteomics》2023,23(7-8):2200023
Urinary glycoproteins associated with aggressive prostate cancer (AG-PCa) were previously reported using post-digital rectal examination (DRE) urine specimens. To explore the potential of using pre-DRE urine specimens for detecting AG-PCa, we compared glycoproteins between pre- and post-DRE urine specimens, verified the previously identified post-DRE AG-PCa-associated urinary glycoproteins in pre-DRE urine specimens, and explored potential new glycoproteins for AG-PCa detection in pre-DRE urine specimens. Quantitative glycoproteomic data were acquired for 154 pre-DRE urine specimens from 41 patients with no cancer at biopsy, 48 patients with non-AG-PCa (Gleason score = 6), and 65 patients with AG-PCa (Gleason score 7 or above). Compared to glycopeptides from the post-DRE urine data, humoral immunity-related proteins were enriched in pre-DRE urine samples, whereas cell mediated immune response proteins were enriched in post-DRE urine samples. Analyses of AG-PCa-associated glycoproteins from pre-DRE urine revealed that the three urinary glycoproteins, prostate-specific antigen (PSA), prostatic acid phosphatase (ACPP), and CD97 antigen (CD97) that were previously identified in post-DRE urine samples, were also observed as AG-PCa associated glycoproteins in pre-DRE urine. In addition, we identified three new glycoproteins, fibrillin 1 (FBN1), vitronectin (VTN), and hemicentin 2 (HMCN2), to be potentially associated with AG-PCa in pre-DRE urine specimens. In summary, glycoprotein profiles differ between pre- and post-DRE urine specimens. The identified AG-PCa-associated glycoproteins may be further evaluated in large cohort of pre-DRE urine specimens for detecting clinically significant PCa. 相似文献
238.
Overproduction of the Bacillus sphaericus R modification methylase in Escherichia coli and its purification to homogeneity 总被引:1,自引:0,他引:1
A DNA fragment containing the information coding for the GGCC-specific Bacillus sphaericus R modification methylase, BspR, was inserted into plasmid vector pKK223-3 under the control of the strong and inducible tac promoter, and transformed into Escherichia coli HB101. Upon induction this strain accumulated the methylase enzyme (while cell growth was inhibited) up to several percent of total cellular protein. Homogeneous methylase could be prepared in three purification steps. 相似文献
239.
Gyorgy Csako Rene Costello Ejaz A Shamim Terrance P O'Hanlon Anthony Tran Daniel J Clauw H James Williams Frederick W Miller 《Arthritis research & therapy》2007,9(5):R95
Prior studies have suggested abnormalities of serum proteins, including paraproteins, in women with silicone implants but
did not control for the presence of connective-tissue disease (CTD). This retrospective case–control study, performed in tertiary-care
academic centers, assessed possible alterations of serum proteins, including paraproteins, in such a population. Seventy-four
women with silicone implants who subsequently developed CTD, and 74 age-matched and CTD-matched women without silicone implants,
were assessed in the primary study; other groups were used for additional comparisons. Routine serum protein determinations
and high-sensitivity protein electrophoresis and immunofixation electrophoresis were performed for detection of paraproteins.
Women with silicone implants, either with or without CTD, had significantly lower serum total protein and α1-globulin, α2-globulin, β-globulin, γ-globulin, and IgG levels compared with those without silicone implants. There was no significant
difference, however, in the frequency of paraproteinemia between women with silicone implants and CTD (9.5%) and age-matched
and CTD-matched women without silicone implants (5.4%) (odds ratio, 1.82; 95% confidence interval, 0.51–6.45). Paraprotein
isotypes were similar in the two groups, and the clinical characteristics of the 13 women with paraproteinemia were comparable
with an independent population of 10 women with silicone breast implants, CTD, and previously diagnosed monoclonal gammopathies.
In summary, this first comprehensive study of serum proteins in women with silicone implants and CTD found no substantially
increased risk of monoclonal gammopathy. Women with silicone implants, however, had unexpectedly low serum globulin and immunoglobulin
levels, with or without the subsequent development of CTD. The causes and clinical implications of these findings require
further investigation. 相似文献
240.