全文获取类型
收费全文 | 1031篇 |
免费 | 75篇 |
出版年
2023年 | 8篇 |
2022年 | 12篇 |
2021年 | 28篇 |
2020年 | 17篇 |
2019年 | 28篇 |
2018年 | 20篇 |
2017年 | 16篇 |
2016年 | 42篇 |
2015年 | 60篇 |
2014年 | 60篇 |
2013年 | 84篇 |
2012年 | 77篇 |
2011年 | 103篇 |
2010年 | 57篇 |
2009年 | 43篇 |
2008年 | 64篇 |
2007年 | 72篇 |
2006年 | 52篇 |
2005年 | 68篇 |
2004年 | 55篇 |
2003年 | 31篇 |
2002年 | 41篇 |
2001年 | 5篇 |
2000年 | 3篇 |
1999年 | 2篇 |
1998年 | 3篇 |
1997年 | 7篇 |
1996年 | 3篇 |
1995年 | 1篇 |
1994年 | 5篇 |
1993年 | 2篇 |
1992年 | 4篇 |
1991年 | 4篇 |
1990年 | 6篇 |
1989年 | 2篇 |
1988年 | 3篇 |
1987年 | 3篇 |
1986年 | 2篇 |
1985年 | 7篇 |
1983年 | 1篇 |
1980年 | 1篇 |
1976年 | 1篇 |
1975年 | 1篇 |
1974年 | 1篇 |
1957年 | 1篇 |
排序方式: 共有1106条查询结果,搜索用时 15 毫秒
1.
2.
Kinetic parameters of the protein tyrosine kinase activity of EGF-receptor mutants with individually altered autophosphorylation sites. 总被引:27,自引:4,他引:23
下载免费PDF全文
![点击此处可从《The EMBO journal》网站下载免费的PDF全文](/ch/ext_images/free.gif)
A Honegger T J Dull D Szapary A Komoriya R Kris A Ullrich J Schlessinger 《The EMBO journal》1988,7(10):3053-3060
Epidermal growth factor (EGF)-receptor mutants in which individual autophosphorylation sites (Tyr1068, Tyr1148 or Tyr1173) have been replaced by phenylalanine residues were expressed in NIH-3T3 cells lacking endogenous EGF-receptors. Kinetic parameters of the kinase of wild-type and mutant receptors were compared. Both wild-type and mutant EGF-receptors had a Km(ATP) 1-3 microM for the autophosphorylation reaction, and a Km(ATP) of 3-7 microM for the phosphorylation of a peptide substrate. These are similar to the Km(ATP) values reported for EGF-receptor of A431 cells. A synthetic peptide representing the major in vitro autophosphorylation site Tyr1173 of the EGF-receptor (KGSTAENAEYLRV) was phosphorylated by wild-type receptor with a Km of 110-130 microM, and the peptide inhibited autophosphorylation with a Ki of 150 microM. Mutant EGF-receptors phosphorylated the peptide substrate with a Km of 70-100 microM. A similar decrease of Km (substrate) was obtained when the phosphorylation experiments were performed with the commonly applied substrates angiotensin II and a peptide derived from c-src. The Km of angiotensin II phosphorylation was reduced from 1100 microM for wild-type receptor to 890 microM for mutant receptor and for c-src peptide from 1010 microM to 770 microM respectively. The Vmax of the kinase was dependent on receptor concentration, but was not significantly affected by the mutation. Analogs of the Tyr1173 peptide in which the tyrosine residue was replaced by either a phenylalanine or an alanine residue also inhibited autophosphorylation with Ki of 650-750 microM. These analyses show that alterations of individual autophosphorylation sites do not have a major effect on kinase activity.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
3.
Jeong-Yau Ho Rob Weide Helen M. Ma Monique F. van Wordragen Kris N. Lambert Maarten Koornneef Pim Zabel Valerie M. Williamson 《The Plant journal : for cell and molecular biology》1992,2(6):971-982
A dominant allele at the Mi locus on chromosome 6 of tomato (Lycopersicon esculentum Mill) confers resistance to three species of root-knot nematodes (Meloidogyne). The resistance, which is associated with a localized necrotic response, was originally introduced into tomato from the wild species Lycopersicon peruvianum. As a step towards the molecular cloning of Mi, we have identified closely linked DNA markers from both cDNA and genomic DNA libraries as restriction fragment length polymorphisms (RFLPs). DNA from tomato populations segregating for nematode resistance was analyzed to generate a high-resolution genetic map of this region. Additional information on gene order was obtained by comparing the size of the introgressed L. peruvianum chromosomal segment within a collection of nematode-resistant tomato lines. Among the four cDNA markers that are tightly linked to Mi, three are dominant, i.e. L. peruvianum-specific. One cDNA marker corresponds to a gene family comprising 20-30 members, one of which is diagnostic for all nematode-resistant genotypes tested. The presence of non-homologous sequences around the Mi gene may contribute to the suppression of recombination in this region of the genome in crosses heterozygous for Mi. The potential of 'walking' from closely linked markers to Mi is discussed. 相似文献
4.
Antibodies against a synthetic peptide as a probe for the kinase activity of the avian EGF receptor and v-erbB protein 总被引:77,自引:0,他引:77
The transforming protein v-erbB of avian erythroblastosis virus (AEV) displays extensive sequence homology with the presumptive protein-tyrosine kinase domain of the human EGF receptor and with the src protein-tyrosine kinase family of oncogenes. However, no kinase activity has previously been demonstrated for the v-erbB protein. Here antibodies generated against a synthetic peptide from the C terminus of human EGF receptor are shown to immunoprecipitate the EGF receptor from human and avian cells, as well as the v-erbB proteins from AEV-transformed cells that become phosphorylated on tyrosine residues upon the addition of gamma-32P-ATP. The immunoprecipitates are also able to phosphorylate exogenous tyrosine-containing substrates. Hence, it is likely that both avian EGF receptor and v-erbB proteins are protein tyrosine-specific protein kinases. Since the kinase activity of v-erbB protein cannot be regulated by EGF, it is proposed that the tyrosine protein kinase function of v-erbB may be constitutively activated. 相似文献
5.
6.
Anti-epidermal growth factor receptor antibodies inhibit the autocrine-stimulated growth of MDA-468 human breast cancer cells 总被引:5,自引:0,他引:5
B W Ennis E M Valverius S E Bates M E Lippman F Bellot R Kris J Schlessinger H Masui A Goldenberg J Mendelsohn 《Molecular endocrinology (Baltimore, Md.)》1989,3(11):1830-1838
The response of malignant and nonmalignant human breast cell lines to the growth inhibitory effects of monoclonal antibodies against the epidermal growth factor (EGF) receptor was studied. A series of human breast cell lines, which express EGF receptor, were used: MDA-468, MDA-231, and Hs578T human breast cancer cells and the transformed human mammary epithelial cell lines 184A1N4 and 184A1N4-T that have been benzo[a]pyrene immortalized and further transformed with SV40T, respectively. Four antibodies of two different classes were tested: 225 immunoglobulin G (IgG), 108.4 IgG, 96 immunoglobulin M (IgM), and 42 IgM. All four antibodies inhibited the anchorage-dependent and -independent, EGF-stimulated growth of 184A1N4 and 184A1N4-T cells, respectively, and this growth inhibition could be reversed by the addition of increasing concentrations of EGF. In contrast, the antibodies inhibited the anchorage-dependent and -independent growth of MDA-468 cells in the absence of exogenous EGF suggesting that the antibodies were acting to block access of an endogenously produced ligand to the EGF receptor. In the presence of antibody and increasing concentrations of EGF, MDA-468 cell growth was first stimulated then inhibited as the EGF concentration increased, thus, uncovering the growth stimulatory potential of low concentrations of EGF in these cells. Data is presented that indicates MDA-468 cells secrete a transforming growth factor with autocrine growth stimulatory capabilities. The growth of MDA-231 and Hs578T cells, which contain activated ras oncogenes, was not inhibited by the antibodies and the growth of these cell lines was not stimulated by EGF. Of the cell lines studied only MDA-468 cells appear to possess an autocrine growth stimulatory capacity. 相似文献
7.
8.
Benzothiadiazole induces disease resistance in Arabidopsis by activation of the systemic acquired resistance signal transduction pathway 总被引:18,自引:6,他引:12
Kay A. Lawton Leslie Friedrich Michelle Hunt Kris Weymann Terrance Delaney Helmut Kessmann Theodor Staub John Ryals 《The Plant journal : for cell and molecular biology》1996,10(1):71-82
Benzothiadiazole (BTH) is a novel chemical activator of disease resistance in tobacco, wheat and other important agricultural plants. In this report, it is shown that BTH works by activating SAR in Arabidopsis thaliana. BTH-treated plants were resistant to infection by turnip crinkle virus, Pseudomonas syringae pv ‘tomato’ DC3000 and Peronospora parasitica. Chemical treatment induced accumulation of mRNAs from the SAR-associated genes, PR-1, PR-2 and PR-5. BTH treatment induced both PR-1 mRNA accumulation and resistance against P. parasitica in the ethylene response mutants, etr1 and ein2, and in the methyl jasmonate-insensitive mutant, jar1, suggesting that BTH action is independent of these plant hormones. BTH treatment also induced both PR-1 mRNA accumulation and P. parasitica resistance in transgenic Arabidopsis plants expressing the nahG gene, suggesting that BTH action does not require salicylic acid accumulation. However, because BTH-treatment failed to induce either PR-1 mRNA accumulation or P. parasitica resistance in the non-inducible immunity mutant, nim1, it appears that BTH activates the SAR signal transduction pathway. 相似文献
9.
Mass spectrometry-driven proteomics is increasingly relying on quantitative analyses for biological discoveries. As a result, different methods and algorithms have been developed to perform relative or absolute quantification based on mass spectrometry data. One of the most popular quantification methods are the so-called label-free approaches, which require no special sample processing, and can even be applied retroactively to existing data sets. Of these label-free methods, the MS/MS-based approaches are most often applied, mainly because of their inherent simplicity as compared to MS-based methods. The main application of these approaches is the determination of relative protein amounts between different samples, expressed as protein ratios. However, as we demonstrate here, there are some issues with the reproducibility across replicates of these protein ratio sets obtained from the various MS/MS-based label-free methods, indicating that the existing methods are not optimally robust. We therefore present two new methods (called RIBAR and xRIBAR) that use the available MS/MS data more effectively, achieving increased robustness. Both the accuracy and the precision of our novel methods are analyzed and compared to the existing methods to illustrate the increased robustness of our new methods over existing ones. 相似文献
10.
Breckpot K Heirman C De Greef C van der Bruggen P Thielemans K 《Journal of immunology (Baltimore, Md. : 1950)》2004,172(4):2232-2237
Antigens encoded by MAGE genes are of particular interest for cancer immunotherapy because they are tumor specific and shared by tumors of different histological types. Several clinical trials are in progress with MAGE peptides, proteins, recombinant poxviruses, and dendritic cells (DC) pulsed with peptides or proteins. The use of gene-modified DC would offer the major advantage of a long-lasting expression of the transgene and a large array of antigenic peptides that fit into the different HLA molecules of the patient. In this study, we tested the ability of gene-modified DC to prime rare Ag-specific T cells, and we identified a new antigenic peptide of clinical interest. CD8(+) T lymphocytes from an individual without cancer were stimulated with monocyte-derived DC, which were infected with a second-generation lentiviral vector encoding MAGE-3. A CTL clone was isolated that recognized peptide EGDCAPEEK presented by HLA-Cw7 molecules, which are expressed by >40% of Caucasians. Interestingly, this new tumor-specific antigenic peptide corresponds to position 212-220 of MAGE-2, -3, -6, and -12. HLA-Cw7 tumor cell lines expressing one of these MAGE genes were lysed by the CTL, indicating that the peptide is efficiently processed in tumor cells and can therefore be used as target for antitumoral vaccination. The risk of tumor escape due to appearance of Ag-loss variants should be reduced by the fact that the peptide is encoded by several MAGE genes. 相似文献