全文获取类型
收费全文 | 16527篇 |
免费 | 1250篇 |
国内免费 | 1188篇 |
出版年
2024年 | 42篇 |
2023年 | 238篇 |
2022年 | 571篇 |
2021年 | 948篇 |
2020年 | 570篇 |
2019年 | 760篇 |
2018年 | 758篇 |
2017年 | 557篇 |
2016年 | 786篇 |
2015年 | 1036篇 |
2014年 | 1287篇 |
2013年 | 1413篇 |
2012年 | 1506篇 |
2011年 | 1364篇 |
2010年 | 826篇 |
2009年 | 742篇 |
2008年 | 843篇 |
2007年 | 702篇 |
2006年 | 561篇 |
2005年 | 504篇 |
2004年 | 417篇 |
2003年 | 362篇 |
2002年 | 268篇 |
2001年 | 250篇 |
2000年 | 222篇 |
1999年 | 231篇 |
1998年 | 158篇 |
1997年 | 135篇 |
1996年 | 121篇 |
1995年 | 110篇 |
1994年 | 103篇 |
1993年 | 87篇 |
1992年 | 102篇 |
1991年 | 100篇 |
1990年 | 53篇 |
1989年 | 55篇 |
1988年 | 41篇 |
1987年 | 32篇 |
1986年 | 22篇 |
1985年 | 27篇 |
1984年 | 23篇 |
1983年 | 15篇 |
1982年 | 7篇 |
1981年 | 4篇 |
1980年 | 3篇 |
1979年 | 3篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
991.
992.
Ying Chang Bin Li Xiaolin Xu Ling Shen Haixia Bai Fei Gao Zhibao Zhang Jost B. Jonas 《PloS one》2016,11(2)
Purpose
To explore expression and function of astrocyte elevated gene-1 (AEG-1) in human retinoblastoma (RB).Methods
The expression of AEG-1 in histological sections of human RBs and in RB cell lines was examined using immunohistochemical staining and RT-PCR and Western blotting respectively. We knocked down AEG-1 gene levels by AEG-1-siRNA lentivirus transfection of human RB cell lines SO-RB50 and Y79, and using an MTT assay, we assessed the role of AEG-1 on RB cell proliferation. The biological significance of lentivirus transfection induced AEG-1 down-regulation was examined by assessing the apoptosis rate in the transfected RB cells by Annexin V-APC staining and flow cytometry. We additionally measured the expression of Bcl-2, Bax, cleaved-caspase-3 and caspase-3, and the phosphorylation and non-phosphorylation alternation of MAPKs.Results
AEG-1 expression was detected to be strongly positive in the histological slides of 35 out of 54 (65%) patients with RB. AEG-1 expression increased significantly (P<0.05) with tumor stage. In the RB cell lines SO-RB50, Y79 and WERI-RB1 as compared with retinal pigment epithelium cells, expression of AEG-1 mRNA and AEG-1 protein was significantly higher. In AEG-1-siRNA lentivirus transfected cell cultures as compared with negative control lentivirus transfected cell cultures, levels of AEG-1 mRNA and of AEG-1 protein (P<0.05) and cell growth rates (P<0.01) were significantly lower, and apoptosis rate (P<0.001), Bax/Bcl-2 ratio and cleaved-caspase-3 protein level were significantly increased. The P-ERK/ERK ratio was significantly decreased in the AEG-1-siRNA lentivirus transfected cell lines.Conclusions
Expression of AEG-1 was associated with RB, in histological slides of patients and in cell culture experiments. Lentivirus transfection induced knockdown of AEG-1 had a tumor suppressive effect, potentially by tumor cell apoptosis induction through inhibition of ERK. 相似文献993.
The Effect of N Fertilizer Placement on the Fate of Urea-15N and Yield of Winter Wheat in Southeast China 总被引:3,自引:0,他引:3
A field micro-plot experiment using nitrogen isotope (15N) labeling was conducted to determine the effects of placement methods (broadcast and band) and N rates (60, 150 and 240 kg ha–1) on the fate of urea-15N in the wheat–soil system in Guangde County of Anhui Province, China. N fertilizer applied in bands increased grain yield by 15% compared with broadcast application. The N fertilizer application rate had a significant effect on grain yield, straw yield and aboveground biomass, as well as on N uptake and N concentration of wheat. The recovery of urea-15N was a little higher for broadcast (34.0–39.0%) than for band treatment (31.2–38.2%). Most of the soil residual N was retained in the 0–20 cm soil layer. At the N rates of 60 and 240 kg ha–1, the residual 15N was higher for band (34.4 and 108.7 kg ha–1, respectively) than for broadcast application (29.6 and 88.4 kg ha–1, respectively). Compared with broadcast treatment, banded placement of N fertilizer decreased the N loss in the wheat–soil system. Band application one time is an alternative N management practice for winter wheat in this region. 相似文献
994.
995.
ZDHHC16 modulates FGF/ERK dependent proliferation of neural stem/progenitor cells in the zebrafish telencephalon
下载免费PDF全文
![点击此处可从《Developmental neurobiology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Fen Wang Ming Gao Yang Yang Zhaoxia Du Chen Wang Yao Yao Kun He Aijun Hao 《Developmental neurobiology》2016,76(9):1014-1028
In vertebrates, neural stem/progenitor cells (NSPCs) maintenance is critical for nervous system development and homeostasis. However, the molecular mechanisms underlying the maintenance of NSPCs have not been fully elucidated. Here, we demonstrated that zebrafish ZDHHC16, a DHHC encoding protein, which was related to protein palmitoylation after translation, was expressed in the developing forebrain, and especially in the telencephalon. Loss‐ and gain‐of‐function studies showed that ZDHHC16 played a crucial role in the regualtion of NSPCs proliferation during zebrafish telencephalic development, via a mechanism dependent on its palmitoyltransferase activity. Further analyses showed that the inhibition of ZDHHC16 led to inactivation of the FGF/ERK signaling pathway during telencephalic NSPCs proliferation and maintenance. Taken together, our results suggest that ZDHHC16 activity is essential for early NSPCs proliferation where it acts to activate the FGF/ERK network, allowing for the initiation of proliferation –regulated gene expression programs. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 76: 1014–1028, 2016 相似文献
996.
Li Peng Kimberly Cook Linda Xu Li Cheng Melissa Damschroder Changshou Gao 《MABS-AUSTIN》2016,8(8):1598-1605
Inhibitors of tumor necrosis factor-α converting enzyme (TACE) have potential as therapeutics for various diseases. Many small molecule inhibitors, however, exhibit poor specificity profiles because they target the highly conserved catalytic cleft of TACE. We report for the first time the molecular interaction of a highly specific anti-TACE antagonistic antibody (MEDI3622). We characterized the binding of MEDI3622 using mutagenesis, as well as structural modeling and docking approaches. We show that MEDI3622 recognizes a unique surface loop of sIVa-sIVb β-hairpin on TACE M-domain, but does not interact with the conserved catalytic cleft or its nearby regions. The exquisite specificity of MEDI3622 is mediated by this distinct structural feature on the TACE M-domain. These findings may aid the design of antibody therapies against TACE. 相似文献
997.
998.
999.
Esther H. D. Carlitz Robert Miller Clemens Kirschbaum Wei Gao Daniel C. H?nni Carel P. van Schaik 《PloS one》2016,11(4)
Non-human primates face major environmental changes due to increased human impacts all over the world. Although some species are able to survive in certain landscapes with anthropogenic impact, their long-term viability and fitness may be decreased due to chronic stress. Here we assessed long-term stress levels through cortisol analysis in chimpanzee hair obtained from sleeping nests in northwestern Uganda, in order to estimate welfare in the context of ecotourism, forest fragmentation with human-wildlife conflicts, and illegal logging with hunting activity (albeit not of primates), compared with a control without human contact or conflict. Concerning methodological issues, season [F(2,129) = 37.4, p < 0.0001, r2 = 0.18] and the age of nests [F(2,178) = 20.3, p < 0.0001, r2 = 0.11] significantly predicted hair cortisol concentrations (HCC). With regard to effects of anthropogenic impacts, our results neither showed elevation of HCC due to ecotourism, nor due to illegal logging compared to their control groups. We did, however, find significantly increased HCC in the fragment group compared to chimpanzees living in a nearby intact forest [F(1,88) = 5.0, p = 0.03, r2 = 0.20]. In conclusion, our results suggest that hair cortisol analysis is a powerful tool that can help understanding the impact of anthropogenic disturbances on chimpanzee well-being and could be applied to other great ape species. 相似文献
1000.
Jintang Sun Meixiang Yang Yanli Ban Wenjuan Gao Bingfeng Song Yang Wang Yun Zhang Qianqian Shao Beihua Kong Xun Qu 《PloS one》2016,11(1)
NK cells accumulate at the maternal-fetal interface (MFI) and play essential roles in maintaining immune tolerance during pregnancy. The mechanisms that facilitate NK cells tolerance to fetal tissue are largely unknown. T cell Ig and mucin domain-containing protein 3 (Tim-3) is a newly defined molecule with essential immunological function in many physiological and pathological processes. Recent study showed that Tim-3 was involved in the regulation of immune tolerance at MFI. However, whether Tim-3 regulates NK cells cytotoxicity toward trophoblasts is unclear. Here, we showed Tim-3 was mainly expressed by decidual NK cells (dNK) and Tim-3 level in dNK was higher than peripheral NK cells (pNK). Tim-3+ dNK expressed more levels of mature markers CD94 and CD69 than Tim-3- dNK cells and blocking Tim-3 significantly inhibited dNK IFN-γ and TNF-α secretion. Furthermore, we found TGF-β1 may contribute to such up-regulation of Tim-3 in NK cells. Interestingly, blocking Tim-3 enhanced NK cytotoxicity toward trophoblast cell line HTR-8 but not K562. We found HTR-8 expressed Tim-3 ligand Galectin-9, in contrast K562 did not. Small interfering RNA-mediated silencing of Galectin-9 expression enhanced NK cytotoxicity toward HTR-8. We further showed Tim-3/Galecin-9 inhibited NK cytotoxicity toward trophoblast partially via impairing the degranulation process. In addition, clinical data showed that abnormal Tim-3 level on pNK might be associated with recurrent spontaneous abortion (RSA). Thus, our data demonstrate Tim-3/Galectin-9 pathway maintains local tolerance by suppressing NK cytotoxicity toward trophoblasts which may represent a new immunologic tolerance mechanism at MFI. 相似文献