全文获取类型
收费全文 | 391篇 |
免费 | 20篇 |
国内免费 | 1篇 |
专业分类
412篇 |
出版年
2023年 | 3篇 |
2022年 | 5篇 |
2021年 | 11篇 |
2020年 | 14篇 |
2019年 | 9篇 |
2018年 | 12篇 |
2017年 | 6篇 |
2016年 | 11篇 |
2015年 | 20篇 |
2014年 | 16篇 |
2013年 | 30篇 |
2012年 | 26篇 |
2011年 | 33篇 |
2010年 | 21篇 |
2009年 | 25篇 |
2008年 | 30篇 |
2007年 | 29篇 |
2006年 | 20篇 |
2005年 | 14篇 |
2004年 | 20篇 |
2003年 | 16篇 |
2002年 | 15篇 |
2001年 | 3篇 |
2000年 | 2篇 |
1999年 | 1篇 |
1998年 | 2篇 |
1993年 | 2篇 |
1992年 | 3篇 |
1990年 | 3篇 |
1987年 | 1篇 |
1986年 | 1篇 |
1984年 | 1篇 |
1982年 | 2篇 |
1977年 | 2篇 |
1976年 | 3篇 |
排序方式: 共有412条查询结果,搜索用时 0 毫秒
1.
2.
Dermal β-catenin activity in response to epidermal Wnt ligands is required for fibroblast proliferation and hair follicle initiation 总被引:1,自引:0,他引:1
Dermal fibroblasts are required for structural integrity of the skin and for hair follicle development. Uniform Wnt signaling activity is present in dermal fibroblast precursors preceding hair follicle initiation, but the functional requirement of dermal Wnt signaling at early stages of skin differentiation and patterning remains largely uncharacterized. We show in mice that epidermal Wnt ligands are required for uniform dermal Wnt signaling/β-catenin activity and regulate fibroblast cell proliferation and initiation of hair follicle placodes. In the absence of dermal Wnt signaling/β-catenin activity, patterned upregulation of epidermal β-catenin activity and Edar expression are absent. Conversely, forced activation of β-catenin signaling leads to the formation of thickened dermis, enlarged epidermal placodes and dermal condensates that result in prematurely differentiated enlarged hair follicles. These data reveal functional roles for dermal Wnt signaling/β-catenin in fibroblast proliferation and in the epidermal hair follicle initiation program. 相似文献
3.
An expression vector constructed from genes of Pichia pastoris was applied for heterologous gene expression in Saccharomyces cerevisiae. Recombinant hepatitis B surface antigen was synthesized by cloning hepatitis B virus ‘S’ gene under the control of glyceraldehyde-3-phosphate
dehydrogenase (GAP) promoter of Pichia pastoris in Saccharomyces cerevisiae. Hepatitis B surface antigen was constitutively expressed, was stable and exhibited ∼20–22 nm particle formation. Stability
and absence of toxicity to the host with the expression vector indicates the expression system can be applied for large-scale
production. 相似文献
4.
Radhika C. Reddy Rebecka Amodei Charles T. Estill Fred Stormshak Mary Meaker Charles E. Roselli 《PloS one》2015,10(6)
Testosterone plays an essential role in sexual differentiation of the male sheep brain. The ovine sexually dimorphic nucleus (oSDN), is 2 to 3 times larger in males than in females, and this sex difference is under the control of testosterone. The effect of testosterone on oSDN volume may result from enhanced expansion of soma areas and/or dendritic fields. To test this hypothesis, cells derived from the hypothalamus-preoptic area (HPOA) and cerebral cortex (CTX) of lamb fetuses were grown in primary culture to examine the direct morphological effects of testosterone on these cellular components. We found that within two days of plating, neurons derived from both the HPOA and CTX extend neuritic processes and express androgen receptors and aromatase immunoreactivity. Both treated and control neurites continue to grow and branch with increasing time in culture. Treatment with testosterone (10 nM) for 3 days significantly (P < 0.05) increased both total neurite outgrowth (35%) and soma size (8%) in the HPOA and outgrowth (21%) and number of branch points (33%) in the CTX. These findings indicate that testosterone-induced somal enlargement and neurite outgrowth in fetal lamb neurons may contribute to the development of a fully masculine sheep brain. 相似文献
5.
Hydrogen peroxide and nitric oxide as signalling molecules in plants 总被引:30,自引:0,他引:30
Neill SJ Desikan R Clarke A Hurst RD Hancock JT 《Journal of experimental botany》2002,53(372):1237-1247
It is now clear that hydrogen peroxide (H(2)O(2)) and nitric oxide (NO) function as signalling molecules in plants. A wide range of abiotic and biotic stresses results in H(2)O(2) generation, from a variety of sources. H(2)O(2) is removed from cells via a number of antioxidant mechanisms, both enzymatic and non-enzymatic. Both biotic and abiotic stresses can induce NO synthesis, but the biosynthetic origins of NO in plants have not yet been resolved. Cellular responses to H(2)O(2) and NO are complex, with considerable cross-talk between responses to several stimuli. In this review the potential roles of H(2)O(2) and NO during various stresses and the signalling pathways they activate are discussed. Key signalling components that might provide targets for enhancing crop production are also identified. 相似文献
6.
Sathish K Padma B Munugalavadla V Bhargavi V Radhika KV Wasia R Sairam M Singh SS 《Cellular signalling》2004,16(5):589-596
Activation of bovine platelets with thrombin and phorbol 12,13-dibutyrate (PDBu) resulted in phosphorylation of profilin on serine. The phosphorylation was inhibited when platelets were pretreated with the PI 3-kinase inhibitor, LY294002, indicating that profilin phosphorylation is a downstream event with respect to PI 3-kinase activation. Phosphorylation of profilin resulted in significant decrease in actin polymerization (16.5%), indicating an increased affinity of phosphoprofilin towards actin. The critical actin monomer concentration (Cc) increased to 260 nM in the presence of phosphoprofilin in comparison with 200 nM in the presence of profilin. The interaction of phosphoprofilin with phosphatidylinositol 4,5-bisphosphate [PI (4,5)-P2] and poly (L-proline) (PLP) was examined by monitoring the quenching of tryptophan fluorescence. Scatchard plot and binding isotherm data obtained revealed no difference in PI (4,5)-P2 binding between profilin and phosphoprofilin (Kd=20.4 microM), while poly (L-proline)-binding studies indicated a sixfold decrease (27.34 microM for profilin and 4.73 microM for phosphoprofilin) in Kd with phosphoprofilin. In vivo studies with platelets indicated an increased association of p85alpha, the regulatory subunit of PI 3-kinase with phosphoprofilin over profilin. Overall, the data presented conclude that profilin phosphorylated under in vivo conditions and phosphorylation depends upon activation of PI 3-kinase. Phosphoprofilin exhibited increased affinity to poly (L-proline) sequences both in vitro and in vivo. 相似文献
7.
8.
JH Shazia Fathima Jayaraman Selvaraj Venkatacalam Sivabalan Umapathy Vidhya Rekha Rajagopal Ponnulakshmi Veeraraghavan Vishnupriya Malathi Kullappan Radhika Nalinakumari Sreekandan Surapaneni Krishna Mohan Periyasamy Vijayalakshmi 《Bioinformation》2021,17(1):212
The mTOR (mammalian or mechanistic Target of Rapamycin) is linked with oral cancer. Therefore, it is of interest to study the molecular docking-based binding of paclitaxel (a FDA approved drug for oral cancer) and its analogues with mTOR. Hence, we report the binding features of 10-Deacetyltaxol, 7-Epi-10-deacetyltaxol, 7-Epi-Taxol and 6alpha-Hydroxypaclitaxel with mTOR for further consideration. 相似文献
9.
Activation of Notch-1 signaling maintains the neoplastic phenotype in human Ras-transformed cells 总被引:27,自引:0,他引:27
Weijzen S Rizzo P Braid M Vaishnav R Jonkheer SM Zlobin A Osborne BA Gottipati S Aster JC Hahn WC Rudolf M Siziopikou K Kast WM Miele L 《Nature medicine》2002,8(9):979-986
Truncated Notch receptors have transforming activity in vitro and in vivo. However, the role of wild-type Notch signaling in neoplastic transformation remains unclear. Ras signaling is deregulated in a large fraction of human malignancies and is a major target for the development of novel cancer treatments. We show that oncogenic Ras activates Notch signaling and that wild-type Notch-1 is necessary to maintain the neoplastic phenotype in Ras-transformed human cells in vitro and in vivo. Oncogenic Ras increases levels and activity of the intracellular form of wild-type Notch-1, and upregulates Notch ligand Delta-1 and also presenilin-1, a protein involved in Notch processing, through a p38-mediated pathway. These observations place Notch signaling among key downstream effectors of oncogenic Ras and suggest that it might be a novel therapeutic target. 相似文献
10.
Tobacco mosaic virus (TMV), a widespread plant pathogen, is found in tobacco (including cigarettes and smokeless tobacco) as well as in many other plants. Plant viruses do not replicate or cause infection in humans or other mammals. This study was done to determine whether exposure to tobacco products induces an immune response to TMV in humans. Using a sandwich ELISA assay, we detected serum anti-TMV antibodies (IgG, IgG1, IgG3, IgG4, IgA, and IgM) in all subjects enrolled in the study (20 healthy smokers, 20 smokeless-tobacco users, and 20 non-smokers). Smokers had a higher level of serum anti-TMV IgG antibodies than non-smokers, while the serum level of anti-TMV IgA from smokeless tobacco users was lower than smokers and non-smokers. Using bioinformatics, we also found that the human protein TOMM40L (an outer mitochondrial membrane 40 homolog – like translocase) contains a strong homology of six contiguous amino acids to the TMV coat protein, and TOMM40L peptide exhibited cross-reactivity with anti-TMV antibodies. People who smoke cigarettes or other tobacco products experience a lower risk of developing Parkinson’s disease, but the mechanism by which this occurs is unclear. Our results showing molecular mimicry between TMV and human TOMM40L raise the question as to whether TMV has a potential role in smokers against Parkinson’s disease development. The potential mechanisms of molecular mimicry between plant viruses and human disease should be further explored. 相似文献