全文获取类型
收费全文 | 5155篇 |
免费 | 378篇 |
国内免费 | 2篇 |
专业分类
5535篇 |
出版年
2024年 | 4篇 |
2023年 | 20篇 |
2022年 | 79篇 |
2021年 | 101篇 |
2020年 | 82篇 |
2019年 | 110篇 |
2018年 | 152篇 |
2017年 | 134篇 |
2016年 | 193篇 |
2015年 | 334篇 |
2014年 | 352篇 |
2013年 | 407篇 |
2012年 | 453篇 |
2011年 | 440篇 |
2010年 | 294篇 |
2009年 | 271篇 |
2008年 | 315篇 |
2007年 | 328篇 |
2006年 | 268篇 |
2005年 | 246篇 |
2004年 | 227篇 |
2003年 | 190篇 |
2002年 | 175篇 |
2001年 | 68篇 |
2000年 | 42篇 |
1999年 | 36篇 |
1998年 | 41篇 |
1997年 | 21篇 |
1996年 | 24篇 |
1995年 | 8篇 |
1994年 | 12篇 |
1993年 | 8篇 |
1992年 | 7篇 |
1991年 | 10篇 |
1990年 | 9篇 |
1989年 | 7篇 |
1988年 | 4篇 |
1987年 | 5篇 |
1985年 | 5篇 |
1983年 | 7篇 |
1982年 | 5篇 |
1981年 | 3篇 |
1980年 | 6篇 |
1979年 | 6篇 |
1978年 | 3篇 |
1977年 | 4篇 |
1975年 | 2篇 |
1974年 | 2篇 |
1971年 | 3篇 |
1966年 | 2篇 |
排序方式: 共有5535条查询结果,搜索用时 0 毫秒
91.
Lee SY Chun MR Kim DJ Kim JW 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2006,839(1-2):124-129
We have developed a simple, rapid, and accurate HPLC-MS/MS method for the determination of iohexol in serum. The column used was a Zorbax Eclipse XDB-C8 (100 mm x 2.1 mm i.d., 3.5 microm). Mobile phases consisted of water containing 2mM ammonium acetate and 0.1% formic acid (A) and methanol containing 2 mM ammonium acetate and 0.1% formic acid (B). After simple protein precipitation with ZnSO4, serum samples were mixed with I.S. (bromperidol) and centrifuged for 3 min. The obtained extraction recovery at three levels was 94.6-107.4%. Quantitative analysis was performed in the multiple reaction-monitoring mode (m/z 822.0-->804.0 for iohexol, 420.1-->122.7 for I.S.) with the total running time of 3 min for each sample. The assay was linear between 0.5 and 1500 microg/mL (r2 > 0.997). The intra- and inter-assay coefficient of variations were 2.4-6.2% and 5.5-6.5%, respectively. Our method provided sufficient analytical range and specificity for the 210 clinical samples analyzed. 相似文献
92.
Hye Won Lee Chanho Park Je-Gun Joung Minyong Kang Yun Shin Chung Won Joon Oh Seon-Yong Yeom Woong-Yang Park Tae Jin Kim Seong Il Seo 《Current issues in molecular biology》2021,43(1):226
Due to the highly immunogenic nature of renal cell carcinoma (RCC), the tumor microenvironment (TME) is enriched with various innate and adaptive immune subsets. In particular, gamma-delta (γδ) T cells can act as potent attractive mediators of adoptive cell transfer immunotherapy because of their unique properties such as non-reliance on major histocompatibility complex expression, their ability to infiltrate human tumors and recognize tumor antigens, relative insensitivity to immune checkpoint molecules, and broad tumor cytotoxicity. Therefore, it is now critical to better characterize human γδ T-cell subsets and their mechanisms in RCCs, especially the stage of differentiation. In this study, we aimed to identify γδ T cells that might have adaptive responses against RCC progression. We characterized γδ T cells in peripheral blood and tumor-infiltrating lymphocytes (TILs) in freshly resected tumor specimens from 20 RCC patients. Furthermore, we performed a gene set enrichment analysis on RNA-sequencing data from The Cancer Genome Atlas (TCGA) derived from normal kidneys and RCC tumors to ascertain the association between γδ T-cell infiltration and anti-cancer immune activity. Notably, RCC-infiltrating CD3low Vγ9Vδ1 T cells with a terminally differentiated effector memory phenotype with up-regulated activation/exhaustion molecules were newly detected as predominant TILs, and the cytotoxic activity of these cells against RCC was confirmed in vitro. In an additional analysis of the TCGA RCC dataset, γδ T-cell enrichment scores correlated strongly with those for CTLs, Th1 cells, “exhausted” T cells, and M1 macrophages, suggesting active involvement of γδ T cells in anti-tumor rather than pro-tumor activity, and Vδ1 cells were more abundant than Vδ2 or Vδ3 cells in RCC tumor samples. Thus, we posit that Vγ9Vδ1 T cells may represent an excellent candidate for adoptive immunotherapy in RCC patients with a high risk of relapse after surgery. 相似文献
93.
94.
Proteomic analysis of differentially expressed proteins induced by rice blast fungus and elicitor in suspension-cultured rice cells 总被引:1,自引:0,他引:1
We used two-dimensional electrophoresis (2-DE) and other proteomic approaches to identify proteins expressed in suspension-cultured rice cells in response to the rice blast fungus, Magnaporthe grisea. Proteins were extracted from suspension-cultured cells at 24 and 48 h after rice blast fungus inoculation or treatment with elicitor or other signal molecules such as jasmonic acid (JA), salicylic acid, and H(2)O(2). The proteins were then polyethylene glycol fractionated before separation by 2-DE. Fourteen protein spots were induced or increased by the treatments, which we analyzed by N-terminal or internal amino acid sequencing. Twelve proteins from six different genes were identified. Rice pathogen-related protein class 10 (OsPR-10), isoflavone reductase like protein, beta-glucosidase, and putative receptor-like protein kinase were among those induced by rice blast fungus; these have not previously been reported in suspension-cultured rice cells. Six isoforms of probenazole-inducible protein (PBZ1) and two isoforms of salt-induced protein (SalT) that responded to blast fungus, elicitor, and JA were also resolved on a 2-DE gel and identified by proteome analysis. The expression level of these induced proteins both in suspension-cultured cells and in leaves of whole plants was analyzed by Western blot. PBZ1, OsPR-10, and SalT proteins from incompatible reactions were induced earlier and to a greater extent than those in compatible reactions. Proteome analysis can thus distinguish differences in the timing and amount of protein expression induced by pathogens and other signal molecules in incompatible and compatible interactions. 相似文献
95.
GAzer: gene set analyzer 总被引:1,自引:0,他引:1
Kim SB Yang S Kim SK Kim SC Woo HG Volsky DJ Kim SY Chu IS 《Bioinformatics (Oxford, England)》2007,23(13):1697-1699
Gene Set Analyzer (GAzer) is a web-based integrated gene set analysis tool covering previously reported parametric and non-parametric models. Based on a simulation test for the reported algorithms, we classified and implemented three main statistical methods consisting of the z-statistic, gene permutation and sample permutation for ten gene set categories including Gene Ontology (GO) for human, mouse, rat and yeast. This tool identifies significantly altered gene sets scored by z-statistics and P-values from the z-test or permutation test and provides q-values and Bonferroni P-values to correct multiple hypothesis testing. GAzer allows users to observe changes in expression of each gene in a gene set or to see the significance of the gene sets containing a gene(s) of interest, thus allowing interactive data analysis both at the gene and gene set level. Moreover, GAzer offers extensive annotation for each gene. AVAILABILITY: The GAzer gene set analyzer is freely available at http://integromics.kobic.re.kr/GAzer/. SUPPLEMENTARY INFORMATION: This can be found on the web page (http://integromics.kobic.re.kr/GAzer/supplement.jsp). 相似文献
96.
Park S Ahn IS Kwon DY Ko BS Jun WK 《Bioscience, biotechnology, and biochemistry》2008,72(11):2815-2823
Ginseng root is known to induce anti-diabetic activity, but the key components involved are unknown. We investigated which major ginsenosides in ginseng enhanced glucose homeostasis by in vitro studies. Rb1 and Rg1 reduced the triglyceride accumulation in 3T3-L1 adipocytes by activating PKA with increased intracellular cAMP. However, the insulin-stimulated glucose uptake was enhanced by Rb1 and Rg1 via activation of phosphatidylinositol-3 kinase. Rb1 and Rg1 promoted glucose-stimulated insulin secretion and cell viability in Min6 cells through PKA which augmented IRS2 expression to enhance insulin/IGF-1 signaling. These results suggest that Rb1 and Rg1 improved glucose homeostasis through the activation of a PKA like glucagon-like peptide-1 receptor agonist. 相似文献
97.
Pandiyan Indiragandhi Rangasamy Anandham Kyounga Kim Woojong Yim Munusamy Madhaiyan Tongmin Sa 《World journal of microbiology & biotechnology》2008,24(7):1037-1045
This study aimed to examine the induction of defense responses in tomato elicited by Methylobacterium
oryzae CBMB20 as a consequence of reduced stress ethylene level possibly through its ACC deaminase activity. Significantly increased
activities of pathogenesis-related (PR) proteins and defense enzymes such as β-1,3-glucanase, phenylalanine ammonia-lyase,
peroxidase and polyphenol oxidase were noted in M. oryzae CBMB20 pretreated and challenged with Pseudomonas syringae pv. tomato (Pst) compared to either control or M. oryzae-treated tomato plants in both growth chamber and greenhouse conditions. Increased PR proteins and defense enzyme activities
were correlated with the reduction of stress ethylene level. M. oryzae CBMB20 reduced the stress ethylene level about 27% and 55% when challenged with Pst, in growth chamber and greenhouse on
day 7 respectively and the effect was comparable to that of the chemical ethylene biosynthesis inhibitor AVG, L-α-(2-aminoethoxyvinyl)-glycine
hydrochloride. As a consequence of reduced stress ethylene level and its effect on defense response in crop plants, the disease
severity was reduced 26% in M. oryzae CBMB20-treated plants challenged with pathogen. Therefore, inoculation of M. oryzae CBMB20 would induce the defense enzymes and contribute to the enhanced resistance of tomato plants against the pathogen Pst. 相似文献
98.
Kim SY Jo HY Kim MH Cha YY Choi SW Shim JH Kim TJ Lee KY 《The Journal of biological chemistry》2008,283(48):33563-33568
Peroxiredoxin 6 (Prdx6) is a bifunctional enzyme with peroxidase activity and Ca2+-independent phospholipase A2 (iPLA2) activity. Here, we report that H2O2-induced cellular toxicity acts through Prdx6 hyperoxidation. Under high concentrations of H2O2 (> 100 microm), Prdx6, and 2-Cys Prdxs were hyperoxidized. Contrary to hyperoxidation of 2-Cys Prdxs, hyperoxidation of Prdx6 was irreversible in vivo. Surprisingly, H2O2-induced cell cycle arrest at the G2/M transition correlated with hyperoxidation and increased iPLA2 activity of Prdx6. This arrest was also associated with up-regulation of p53 and p21 and with down-regulation of cyclin B1. Furthermore, the H2O2-mediated increase in iPLA2 activity was dramatically abolished in a hyperoxidation mutant (C47A), an iPLA2 mutant (S32A), and a double mutant (C47A/S32A) of Prdx6, demonstrating the essential requirement of Prdx6 C47 hyperoxidation for its iPLA2 activity. Together, our results demonstrate that H2O2-mediated hyperoxidation of Prdx6 induces cell cycle arrest at the G2/M transition through up-regulation of iPLA2 activity. 相似文献
99.
100.
The mammalian antizyme (AZ) promotes ubiqutin-independent degradation of ornithine decarboxylase, a key enzyme in polyamine biosynthesis. This study shows that AZ suppression in human lung carcinoma A549 cells caused growth defects and death, but made the cells resistant to DNA damaging agents such as gamma-radiation and cisplatin. In these cells, the cellular redox potential (glutathione/glutathione disulfide [GSH/GSSG] ratio) was increased and thus intracellular reactive oxygen species were severely diminished, which might cause growth defects and cell death. The increase of cellular redox potential was mainly caused by dramatic increase of the cytoplasmic nicotinamide adenine dinucleotide phosphate (NADP)(+)-dependent isocitrate dehydrogenase, which generates the reducing equivalents NADPH. In the AZ-suppressed cells, the hypoxia inducible factor 1alpha (HIF-1alpha) was also increased. As in other cases which showed an increment of HIF-1alpha and the cellular redox potential, the AZ-suppressed cells showed resistance to gamma-radiation and anticancer drugs. Therefore, these facts might be considered as important for the use of radio- and chemotherapy on tumor cells which show an unbalance in their polyamine levels. 相似文献