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101.
Background
Choline kinase is the first enzyme in the CDP-choline pathway that synthesizes phosphatidylcholine, the major phospholipid in eukaryotic cell membranes. In humans, choline kinase exists as three isoforms (CKα1, α2, and β). Specific inhibition of CKα has been reported to selectively kill tumoral cells. Monoclonal and polyclonal antibodies against CKα used in previous studies to detect the level of this isozyme in different cellular or biochemical contexts were able to detect either the α1 or the α2 isoform.Methodology/Principal Findings
In this study, an antiserum against CKα was produced by immunizing rabbits with denatured, purified recombinant CKα2 full-length protein. This antiserum was highly specific for CKα when tested with extracts from different cell lines, and there was no cross reactivity with purified CKβ and other related proteins like human ethanolamine kinases (EK) and yeast choline or ethanolamine kinases. The antiserum simultaneously detected both CKα1 and α2 isoforms in MCF-7 and HepG2 cell extracts, but not in HeLa, HCT-116, and mouse embryonic stem cell extracts. Subsequent protein dot blot assay of total CKα in a human normal/tumor protein array of 30 tissue samples by using the antiserum showed that CKα was not overexpressed in all tumor tissues when compared to their normal counterparts. Most striking differences between tumor and normal CKα expression levels were observed in kidney (11-fold higher in tumor) and liver (15-fold lower in tumor) samples.Conclusion/Significance
Apart from its high sensitivity and specificity, the antiserum produced in this work, which does not require further purification, has the advantage of co-detecting both α1 and α2 isoforms in cell extracts for direct comparison of their expression levels. 相似文献102.
A functionally conserved Zn2Cys6 binuclear cluster transcription factor class regulates necrotrophic effector gene expression and host‐specific virulence of two major Pleosporales fungal pathogens of wheat 下载免费PDF全文
103.
104.
Lowe I Jankuloski L Chao S Chen X See D Dubcovsky J 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》2011,123(1):143-157
A mapping population of 186 recombinant inbred lines developed from a cross between UC1110, an adapted California spring wheat,
and PI610750, a synthetic derivative from CIMMYT’s Wide Cross Program, was evaluated for its response to current California
races of stripe rust (Puccinia striiformis f. sp. tritici) in replicated field trials over four seasons (2007–2010) in the northern Sacramento Valley. A genetic map was constructed
consisting of 1,494 polymorphic probes (SSRs, DArTs, and ESTs) mapped to 558 unique loci, and QTL analysis revealed the presence
of four stripe rust resistance QTL segregating in this population, two from UC1110 (on chromosomes 3BS and 2BS) and two from
PI610750 (5AL and 2AS). The two QTL of largest effects (on 3BS and 5AL) were validated in independent populations and their
intervals narrowed to 2.5 and 5.3 cM, respectively. The 3BS QTL was shown, by allelism test and genotype, to carry a gene
different from the Yr30/Sr2 complex. Mapped position also suggests that the 3BS QTL is associated with a gene different from either Yrns-B1 or YrRub, two stripe rust resistance genes mapped to this region in other studies. The 5AL QTL carries a previously unreported partial
stripe rust resistance gene, designated here as Yr48. This paper discusses the individual contributions to resistance of these four QTL, their epistatic interactions, and their
potential in durable resistance breeding strategies based on combinations of partial resistance genes. 相似文献
105.
Williams-Pritchard G Knight M Hoe LS Headrick JP Peart JN 《American journal of physiology. Heart and circulatory physiology》2011,300(6):H2161-H2168
Transactivation of epidermal growth factor receptor (EGFR) may contribute to specific protective responses (e.g. mediated by δ-opioid, bradykinin, or muscarinic receptors). No studies have assessed EGFR involvement in cardioprotection mediated by adenosine receptors (ARs), and the role of EGFR in ischemic preconditioning (IPC) is unclear. We tested EGFR, matrix metalloproteinase (MMP), and heparin-binding EGF (HB-EGF) dependencies of functional protection via A(1)AR agonism or IPC. Pretreatment of mouse hearts with 100 nM of A(1)AR agonist 2-chloro-N(6)-cyclopentyladenosine (CCPA) or IPC (3 × 1.5-min ischemia/2-min reperfusion) substantially improved recovery from 25-min ischemia, reducing left ventricular diastolic dysfunction up to 50% and nearly doubling pressure development and positive change in pressure over time (+dP/dt). Benefit with both CCPA and IPC was eliminated by inhibitors of EGFR tyrosine kinase (0.3 μM AG1478), MMP (0.3 μM GM6001), or HB-EGF ligand (0.3 ng/ml CRM197), none of which independently altered postischemic outcome. Phosphorylation of myocardial EGFR, Erk1/2, and Akt increased two- to threefold during A(1)AR agonism, with responses blocked by AG1478, GM6001, and CRM197. Studies in HL-1 myocytes confirm A(1)AR-dependent Erk1/2 phosphorylation is negated by AG1478 or GM6001, and reduced with CRM197 (as was Akt activation). These data collectively reveal that A(1)AR- and IPC-mediated functional protection is entirely EGFR and MMP dependent, potentially involving the HB-EGF ligand. Myocardial survival kinase activation (Erk1/2, Akt) by A(1)AR agonism is similarly MMP/HB-EGF/EGFR dependent. Thus MMP-mediated EGFR activation appears essential to cardiac protection and signaling via A(1)ARs and preconditioning. 相似文献
106.
107.
Birgit Eisenhaber Stephan Eisenhaber Toh Yew Kwang Gerhard Grüber 《Cell cycle (Georgetown, Tex.)》2014,13(12):1912-1917
The transamidase subunit GAA1/GPAA1 is predicted to be the enzyme that catalyzes the attachment of the glycosylphosphatidyl (GPI) lipid anchor to the carbonyl intermediate of the substrate protein at the ω-site. Its ~300-amino acid residue lumenal domain is a M28 family metallo-peptide-synthetase with an α/β hydrolase fold, including a central 8-strand β-sheet and a single metal (most likely zinc) ion coordinated by 3 conserved polar residues. Phosphoethanolamine is used as an adaptor to make the non-peptide GPI lipid anchor look chemically similar to the N terminus of a peptide. 相似文献
108.
109.
Yew Kok Lee Shengnan Jin Shiwei Duan Yen Ching Lim Desmond PY Ng Xueqin Michelle Lin George SH Yeo Chunming Ding 《Biological procedures online》2014,16(1):1-9
Background
DNA methylation plays crucial roles in epigenetic gene regulation in normal development and disease pathogenesis. Efficient and accurate quantification of DNA methylation at single base resolution can greatly advance the knowledge of disease mechanisms and be used to identify potential biomarkers. We developed an improved pipeline based on reduced representation bisulfite sequencing (RRBS) for cost-effective genome-wide quantification of DNA methylation at single base resolution. A selection of two restriction enzymes (TaqαI and MspI) enables a more unbiased coverage of genomic regions of different CpG densities. We further developed a highly automated software package to analyze bisulfite sequencing results from the Solexa GAIIx system.Results
With two sequencing lanes, we were able to quantify ~1.8 million individual CpG sites at a minimum sequencing depth of 10. Overall, about 76.7% of CpG islands, 54.9% of CpG island shores and 52.2% of core promoters in the human genome were covered with at least 3 CpG sites per region.Conclusions
With this new pipeline, it is now possible to perform whole-genome DNA methylation analysis at single base resolution for a large number of samples for understanding how DNA methylation and its changes are involved in development, differentiation, and disease pathogenesis. 相似文献110.
Tan To Cheung Ronnie T. P. Poon Kenneth S. H. Chok Albert C. Y. Chan Simon H. Y. Tsang Wing Chiu Dai Thomas C. C. Yau See Ching Chan Sheung Tat Fan Chung Mau Lo 《PloS one》2014,9(4)