全文获取类型
收费全文 | 8167篇 |
免费 | 534篇 |
国内免费 | 4篇 |
专业分类
8705篇 |
出版年
2024年 | 9篇 |
2023年 | 23篇 |
2022年 | 105篇 |
2021年 | 157篇 |
2020年 | 87篇 |
2019年 | 119篇 |
2018年 | 163篇 |
2017年 | 156篇 |
2016年 | 226篇 |
2015年 | 429篇 |
2014年 | 435篇 |
2013年 | 512篇 |
2012年 | 720篇 |
2011年 | 627篇 |
2010年 | 398篇 |
2009年 | 368篇 |
2008年 | 484篇 |
2007年 | 508篇 |
2006年 | 456篇 |
2005年 | 393篇 |
2004年 | 385篇 |
2003年 | 326篇 |
2002年 | 286篇 |
2001年 | 249篇 |
2000年 | 230篇 |
1999年 | 165篇 |
1998年 | 62篇 |
1997年 | 54篇 |
1996年 | 34篇 |
1995年 | 34篇 |
1994年 | 21篇 |
1993年 | 21篇 |
1992年 | 40篇 |
1991年 | 48篇 |
1990年 | 39篇 |
1989年 | 46篇 |
1988年 | 35篇 |
1987年 | 25篇 |
1986年 | 25篇 |
1985年 | 31篇 |
1984年 | 20篇 |
1983年 | 17篇 |
1981年 | 9篇 |
1979年 | 11篇 |
1978年 | 13篇 |
1977年 | 10篇 |
1974年 | 12篇 |
1973年 | 14篇 |
1972年 | 11篇 |
1971年 | 7篇 |
排序方式: 共有8705条查询结果,搜索用时 0 毫秒
81.
Glioblastoma is an aggressive malignant brain tumor that starts in the brain or spine and frequently recurs after anticancer treatment. The development of an accurate diagnostic system combined with effective cancer therapy is essential to improve prognosis of glioma patients. Peptides, produced from phage display, are attractive biomolecules for glioma treatment because of their biostability, nontoxicity, and small size. In this study, we employed phage display methodology to screen for peptides that specifically recognize the target PKCδ as a novel biomarker for glioma. The phage library screening yielded four different peptides displayed on phages with a 20- to 200-pM Kd value for the recombinant PKCδ catalytic domain. Among these four phage peptides, we selected one to synthesize and tagged it with fluorescein isothiocyanate (FITC) based on the sequence of the PKCδ-binding phage clone. The synthetic peptide showed a relative binding affinity for antibody and localization in the U373 glioma cell. The kinase activity of PKCδ was inhibited by FITC-labeled peptide with an IC50 of 1.4 μM in vitro. Consequently, the peptide found in this study might be a promising therapeutic agent against malignant brain tumor. 相似文献
82.
Sunkyu Choi Kun Cho Kyungmoo Yea Jeonghwa Lee Jeongkwon Kim 《Biochemical and biophysical research communications》2009,383(1):135-140
Hypoxia during the expansion of adipocytes is known to contribute both to the secretion of multiple inflammation-related adipokines as well as to obesity. We therefore investigated the nature of protein changes occurring in adipocytes during hypoxia by observation of the intracellular proteins that are expressed in 3T3-L1 adipocytes. Lysates were utilized for quantitative proteome analysis using isobaric tags for relative and absolute quantitation (iTRAQ) combined with peptide separation by multi-dimensional liquid chromatography. Antioxidants and elongation factors, as well as glycolytic enzymes were increased in hypoxic adipocytes. These changes were supported by similar changes suggested by real-time PCR. The proteins showing changes are all potential targets for revering the mechanism behind the phenomenon of induction of obese adipocytes by hypoxia. This study can therefore aid in defining the proteomic changes that occur in adipocytes in response to oxygen stress, and can further characterize adipocyte metabolism and adaptation to low oxygen conditions. 相似文献
83.
84.
Hyo Je Cho Kyungsun Kim Seo Yean Sohn Ha Yeon Cho Kyung Jin Kim Myung Hee Kim Dockyu Kim Eungbin Kim Beom Sik Kang 《The Journal of biological chemistry》2010,285(45):34643-34652
A meta-cleavage pathway for the aerobic degradation of aromatic hydrocarbons is catalyzed by extradiol dioxygenases via a two-step mechanism: catechol substrate binding and dioxygen incorporation. The binding of substrate triggers the release of water, thereby opening a coordination site for molecular oxygen. The crystal structures of AkbC, a type I extradiol dioxygenase, and the enzyme substrate (3-methylcatechol) complex revealed the substrate binding process of extradiol dioxygenase. AkbC is composed of an N-domain and an active C-domain, which contains iron coordinated by a 2-His-1-carboxylate facial triad motif. The C-domain includes a β-hairpin structure and a C-terminal tail. In substrate-bound AkbC, 3-methylcatechol interacts with the iron via a single hydroxyl group, which represents an intermediate stage in the substrate binding process. Structure-based mutagenesis revealed that the C-terminal tail and β-hairpin form part of the substrate binding pocket that is responsible for substrate specificity by blocking substrate entry. Once a substrate enters the active site, these structural elements also play a role in the correct positioning of the substrate. Based on the results presented here, a putative substrate binding mechanism is proposed. 相似文献
85.
Effect of abscisic acid application on root isoflavonoid concentration and nodulation of wild-type and nodulation-mutant soybean plants 总被引:1,自引:0,他引:1
Isoflavonoids (daidzein, genistein, and coumestrol) are involved in induction of nod genes in Bradyrhizobium japonicum and may be involved in nodule development as well. Abscisic acid (ABA) may also impact nodulation since ABA is reportedly
involved in isoflavonoid synthesis. The current study was conducted to evaluate whether ABA plays a role in differential nodulation
of a hypernodulated soybean (Glycine max L. Merr.) mutant and the Williams parent. Exogenous ABA application resulted in a decrease in nodule number and weight in
both lines. Isoflavonoid concentrations were also markedly decreased in response to ABA application in both inoculated and
noninoculated soybean roots. The inoculation treatment itself resulted in a marked increase in isoflavonoid concentrations
of NOD1-3, regardless of ABA levels, while only slight increases occurred in Williams. The nodule numbers of both soybean
lines across several ABA concentration treatments were highly correlated with the concentration of all three isoflavonoids.
However, differences in internal levels of ABA between lines were not detected when grown in the absence of external ABA additions.
It is concluded that differential nodule expression between the wild type and the hypernodulated mutant is not likely due
to differential ABA synthesis. 相似文献
86.
87.
88.
89.
Drought stress has detrimental effects on plants. Although the abscisic acid (ABA)‐mediated drought response is well established, defensive mechanisms to cope with dehydration‐induced proteotoxicity have been rarely studied. DRR1 was identified as an Arabidopsis drought‐induced gene encoding an ER‐localized RING‐type E3 Ub ligase. Suppression of DRR1 markedly reduced tolerance to drought and proteotoxic stress without altering ABA‐mediated germination and stomatal movement. Proteotoxicity‐ and dehydration‐induced insoluble ubiquitinated protein accumulation was more obvious in DRR1 loss‐of‐function plants than in wild‐type plants. These results suggest that DRR1 is involved in an ABA‐independent drought stress response possibly through the mitigation of dehydration‐induced proteotoxic stress. 相似文献
90.
Jang Hye Jin Choi Ji Yeon Kim Kangjoon Yong Seung Hyun Kim Yeon Wook Kim Song Yee Kim Eun Young Jung Ji Ye Kang Young Ae Park Moo Suk Kim Young Sam Cho Young-Jae Lee Sang Hoon 《Respiratory research》2021,22(1):1-9
IL-35 subunit EBI3 is up-regulated in pulmonary fibrosis tissues. In this study, we investigated the pathological role of EBI3 in pulmonary fibrosis and dissected the underlying molecular mechanism. Bleomycin-induced pulmonary fibrosis mouse model was established, and samples were performed gene expression analyses through RNAseq, qRT-PCR and Western blot. Wild type and EBI3 knockout mice were exposed to bleomycin to investigate the pathological role of IL-35, via lung function and gene expression analyses. Primary lung epithelial cells were used to dissect the regulatory mechanism of EBI3 on STAT1/STAT4 and STAT3. IL-35 was elevated in both human and mouse with pulmonary fibrosis. EBI3 knockdown aggravated the symptoms of pulmonary fibrosis in mice. EBI3 deficiency enhanced the expressions of fibrotic and extracellular matrix-associated genes. Mechanistically, IL-35 activated STAT1 and STAT4, which in turn suppressed DNA enrichment of STAT3 and inhibited the fibrosis process. IL-35 might be one of the potential therapeutic targets for bleomycin-induced pulmonary fibrosis. 相似文献