全文获取类型
收费全文 | 1303篇 |
免费 | 102篇 |
国内免费 | 14篇 |
出版年
2023年 | 9篇 |
2022年 | 17篇 |
2021年 | 31篇 |
2020年 | 34篇 |
2019年 | 35篇 |
2018年 | 45篇 |
2017年 | 35篇 |
2016年 | 58篇 |
2015年 | 77篇 |
2014年 | 72篇 |
2013年 | 112篇 |
2012年 | 100篇 |
2011年 | 96篇 |
2010年 | 58篇 |
2009年 | 53篇 |
2008年 | 65篇 |
2007年 | 63篇 |
2006年 | 61篇 |
2005年 | 53篇 |
2004年 | 45篇 |
2003年 | 40篇 |
2002年 | 44篇 |
2001年 | 21篇 |
2000年 | 21篇 |
1999年 | 8篇 |
1998年 | 15篇 |
1997年 | 10篇 |
1996年 | 7篇 |
1995年 | 6篇 |
1994年 | 9篇 |
1993年 | 6篇 |
1992年 | 10篇 |
1991年 | 10篇 |
1990年 | 6篇 |
1989年 | 4篇 |
1988年 | 10篇 |
1987年 | 6篇 |
1986年 | 9篇 |
1985年 | 11篇 |
1984年 | 6篇 |
1982年 | 3篇 |
1981年 | 3篇 |
1979年 | 3篇 |
1976年 | 3篇 |
1974年 | 3篇 |
1973年 | 7篇 |
1968年 | 2篇 |
1967年 | 2篇 |
1944年 | 2篇 |
1943年 | 2篇 |
排序方式: 共有1419条查询结果,搜索用时 78 毫秒
91.
Thrombospondin-1 suppresses wound healing and granulation tissue formation in the skin of transgenic mice 总被引:20,自引:0,他引:20
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)
Streit M Velasco P Riccardi L Spencer L Brown LF Janes L Lange-Asschenfeldt B Yano K Hawighorst T Iruela-Arispe L Detmar M 《The EMBO journal》2000,19(13):3272-3282
The function of the endogenous angiogenesis inhibitor thrombospondin-1 (TSP-1) in tissue repair has remained controversial. We established transgenic mice with targeted overexpression of TSP-1 in the skin, using a keratin 14 expression cassette. TSP-1 transgenic mice were healthy and fertile, and did not show any major abnormalities of normal skin vascularity, cutaneous vascular architecture, or microvascular permeability. However, healing of full-thickness skin wounds was greatly delayed in TSP-1 transgenic mice and was associated with reduced granulation tissue formation and highly diminished wound angiogenesis. Moreover, TSP-1 potently inhibited fibroblast migration in vivo and in vitro. These findings demonstrate that TSP-1 preferentially interfered with wound healing-associated angiogenesis, rather than with the angiogenesis associated with normal development and skin homeostasis, and suggest that therapeutic application of angiogenesis inhibitors might potentially be associated with impaired wound vascularization and tissue repair. 相似文献
92.
The eukaryotic mRNA decapping protein Dcp1 interacts physically and functionally with the eIF4F translation initiation complex
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)
Dcp1 plays a key role in the mRNA decay process in Saccharomyces cerevisiae, cleaving off the 5' cap to leave an end susceptible to exonucleolytic degradation. The eukaryotic initiation factor complex eIF4F, which in yeast contains the core components eIF4E and eIF4G, uses the cap as a binding site, serving as an initial point of assembly for the translation apparatus, and also binds the poly(A) binding protein Pab1. We show that Dcp1 binds to eIF4G and Pab1 as free proteins, as well as to the complex eIF4E-eIF4G-Pab1. Dcp1 interacts with the N-terminal region of eIF4G but does not compete significantly with eIF4E or Pab1 for binding to eIF4G. Most importantly, eIF4G acts as a function-enhancing recruitment factor for Dcp1. However, eIF4E blocks this effect as a component of the high affinity cap-binding complex eIF4E-eIF4G. Indeed, cooperative enhancement of the eIF4E-cap interaction stabilizes yeast mRNAs in vivo. These data on interactions at the interface between translation and mRNA decay suggest how events at the 5' cap and 3' poly(A) tail might be coupled. 相似文献
93.
94.
Martin ME Hidalgo J Rosa JL Crottet P Velasco A 《The Journal of biological chemistry》2000,275(25):19050-19059
The small GTP-binding protein ADP-ribosylation factor 1 (ARF1) is an essential component of the molecular machinery that catalyzes the formation of membrane-bound transport intermediates. By using an in vitro assay that reproduces recruitment of cytosolic proteins onto purified, high salt-washed Golgi membranes, we have analyzed the role of cAMP-dependent protein kinase A (PKA) on ARF1 incorporation. Addition to this assay of either pure catalytic subunits of PKA (C-PKA) or cAMP increased ARF1 binding. By contrast, ARF1 association was inhibited following C-PKA inactivation with either PKA inhibitory peptide or RIIalpha as well as after cytosol depletion of C-PKA. C-PKA also stimulated recruitment and activation of a recombinant form of human ARF1 in the absence of additional cytosolic components. The binding step could be dissociated from the activation reaction and found to be independent of guanine nucleotides and saturable. This step was stimulated by C-PKA in an ATP-dependent manner. Dephosphorylated Golgi membranes exhibited a decreased ability to recruit ARF1, and this effect was reverted by addition of C-PKA. Following an increase in the intracellular level of cAMP, ARF proteins redistributed from cytosol to the perinuclear Golgi region of intact cells. Collectively, the results show that PKA exerts a key regulatory role in the recruitment of ARF1 onto Golgi membranes. In contrast, PKA modulators did not affect recruitment of beta-COP onto Golgi membranes containing prebound ARF1. 相似文献
95.
Idaira Hueso-Falcón Natalia Girón Pilar Velasco Juan M. Amaro-Luis Angel G. Ravelo Beatriz de las Heras Sonsoles Hortelano Ana Estevez-Braun 《Bioorganic & medicinal chemistry》2010,18(4):1724-1735
Thirty one ent-kaurane derivatives were prepared from kaurenoic acid (1), grandiflorenic acid (16), 15α-acetoxy-kaurenoic acid (26) and 16α-hydroxy-kaurenoic acid (31). They were tested for their ability to inhibit cell viability in the mouse leukemic macrophagic RAW 264.7 cell line. The most effective compounds were 12, 20, 21, and 23. These were selected for further evaluation in other human cancer cell lines such as Hela, HepG2, and HT-29. Similar effects were obtained although RAW 264.7 cells were more sensitive. In addition, these compounds were significantly less cytotoxic in non-transformed cells. The apoptotic potential of the most active compounds was investigated and they were able to induce apoptosis with compound 12 being the best inducer. The caspase-3, -8 and -9 activities were measured. The results obtained showed that compounds 12, 21, and 23 induce apoptosis via the activation of caspase-8, whereas compound 20 induces apoptosis via caspase-9. Immunoblot analysis of the expression of p53, Bax, Bcl-2, Bcl-xl, and IAPs in RAW 264.7 cells was also carried out. When cells were exposed to 5 μM of the different compounds, expression levels of p53 and Bax increased whereas levels of antiapoptotic proteins such as Bc1-2, Bc1-x1, and IAPs decreased. In conclusion, kaurane derivatives (12, 20, 21, and 23) induce apoptosis via both the mitochondrial and membrane death receptor pathways, involving the Bcl-2 family proteins. Taken together these results provide a role of kaurane derivatives as apoptotic inducers in tumor cells. 相似文献
96.
Julián Gómez-Cambronero Susana Velasco JoséM. Mato Mariano Sánchez-Crespo 《Biochimica et Biophysica Acta (BBA)/Molecular Cell Research》1985,845(3):516-519
Incubation of rat splenic microsomes with the catalytic subunit of cyclic AMP-dependent protein kinase in the presence of Mg-ATP stimulated 2-3-fold lyso-platelet-activating factor:acetyltransferase activity. This activation was due to an increase in the of the acetylation reaction, whereas the for acetyl-CoA was not affected. The ATP derivative, AMPPNP, could not replace ATP and preincubation of the microsomes with the heat-stable inhibitor of protein kinase prevented the activation by Mg-ATP obtained in the presence of the protein kinase. Activation of the acetylation reaction by the protein kinase was reversible. Evidence is provided that the reversal of activation is due to dephosphorylation of the enzyme. These data provide evidence that in vitro lyso-platelet-activating factor:acetyltransferase from splenic microsomes is regulated by phosphorylation. 相似文献
97.
Rose Monnerat Erica Martins Cristina Macedo Paulo Queiroz Lilian Pra?a Carlos Marcelo Soares Helio Moreira Isabella Grisi Joseane Silva Mario Soberon Alejandra Bravo 《PloS one》2015,10(4)
Brazil ranked second only to the United States in hectares planted to genetically modified crops in 2013. Recently corn producers in the Cerrado region reported that the control of Spodoptera frugiperda with Bt corn expressing Cry1Fa has decreased, forcing them to use chemicals to reduce the damage caused by this insect pest. A colony of S. frugiperda was established from individuals collected in 2013 from Cry1Fa corn plants (SfBt) in Brazil and shown to have at least more than ten-fold higher resistance levels compared with a susceptible colony (Sflab). Laboratory assays on corn leaves showed that in contrast to SfLab population, the SfBt larvae were able to survive by feeding on Cry1Fa corn leaves. The SfBt population was maintained without selection for eight generations and shown to maintain high levels of resistance to Cry1Fa toxin. SfBt showed higher cross-resistance to Cry1Aa than to Cry1Ab or Cry1Ac toxins. As previously reported, Cry1A toxins competed the binding of Cry1Fa to brush border membrane vesicles (BBMV) from SfLab insects, explaining cross-resistance to Cry1A toxins. In contrast Cry2A toxins did not compete Cry1Fa binding to SfLab-BBMV and no cross-resistance to Cry2A was observed, although Cry2A toxins show low toxicity to S. frugiperda. Bioassays with Cry1AbMod and Cry1AcMod show that they are highly active against both the SfLab and the SfBt populations. The bioassay data reported here show that insects collected from Cry1Fa corn in the Cerrado region were resistant to Cry1Fa suggesting that resistance contributed to field failures of Cry1Fa corn to control S. frugiperda. 相似文献
98.
Daniella Braz Parente Fernando Fernandes Paiva Jaime Araújo Oliveira Neto Lilian Machado-Silva Fatima Aparecida Ferreira Figueiredo Valeria Lanzoni Carlos Frederico Ferreira Campos Pedro Emmanuel Alvarenga Americano do Brasil Marilia de Brito Gomes Renata de Mello Perez Rosana Souza Rodrigues 《PloS one》2015,10(5)
ObjectiveTo evaluate the capability of intravoxel incoherent motion (IVIM) diffusion-weighted imaging (DWI) to assess steatohepatitis and fibrosis determined by histopathology in type 2 diabetic patients.MethodsFifty-nine type 2 diabetic patients (49 women, 10 men; mean age, 54 ± 9 years) were submitted to liver biopsy for the evaluation of non-alcoholic fatty liver disease (NAFLD) and underwent DWI on a 3.0T MR system using 10 b values. Institutional approval and patient consent were obtained. Pure molecular-based (D), perfusion-related (D*), and vascular fraction (f) were calculated using a double exponential model and least squares curve fitting. D, D*, and f were compared between patients with and without steatohepatitis and between patients with and without fibrosis. The variables were compared by using the Ranksum test and Student t-test.ResultsSteatohepatitis was observed in 22 patients and fibrosis in 16 patients. A lower D median (0.70 s/mm2 vs. 0.83 s/mm2, p<0.05) and a lower D* median (34.39 s/mm2 vs. 45.23 s/mm2, p<0.05) were observed among those with steatohepatitis. A lower D median (0.70 s/mm2 vs. 0.82 s/mm2, p<0.05) and a lower D* median (35.01 s/mm2 vs. 44.76 s/mm2, p=0.05) were also observed among those with fibrosis.ConclusionIVIM-DWI has the potential to aid in the characterization of steatohepatitis and fibrosis. 相似文献
99.
In-Kyu Yoon Maria Theresa Alera Catherine B. Lago Ilya A. Tac-An Daisy Villa Stefan Fernandez Butsaya Thaisomboonsuk Chonticha Klungthong Jens W. Levy John Mark Velasco Vito G. Roque Jr. Henrik Salje Louis R. Macareo Laura L. Hermann Ananda Nisalak Anon Srikiatkhachorn 《PLoS neglected tropical diseases》2015,9(5)