全文获取类型
收费全文 | 2760篇 |
免费 | 232篇 |
国内免费 | 1篇 |
专业分类
2993篇 |
出版年
2024年 | 5篇 |
2023年 | 27篇 |
2022年 | 57篇 |
2021年 | 97篇 |
2020年 | 43篇 |
2019年 | 67篇 |
2018年 | 80篇 |
2017年 | 69篇 |
2016年 | 76篇 |
2015年 | 143篇 |
2014年 | 159篇 |
2013年 | 165篇 |
2012年 | 252篇 |
2011年 | 255篇 |
2010年 | 138篇 |
2009年 | 122篇 |
2008年 | 148篇 |
2007年 | 136篇 |
2006年 | 105篇 |
2005年 | 113篇 |
2004年 | 109篇 |
2003年 | 86篇 |
2002年 | 75篇 |
2001年 | 71篇 |
2000年 | 55篇 |
1999年 | 57篇 |
1998年 | 28篇 |
1997年 | 17篇 |
1996年 | 7篇 |
1995年 | 11篇 |
1994年 | 12篇 |
1993年 | 13篇 |
1992年 | 17篇 |
1991年 | 14篇 |
1990年 | 15篇 |
1989年 | 22篇 |
1988年 | 12篇 |
1987年 | 10篇 |
1986年 | 12篇 |
1985年 | 10篇 |
1984年 | 6篇 |
1983年 | 11篇 |
1982年 | 5篇 |
1981年 | 6篇 |
1980年 | 5篇 |
1979年 | 5篇 |
1976年 | 5篇 |
1973年 | 4篇 |
1970年 | 4篇 |
1969年 | 5篇 |
排序方式: 共有2993条查询结果,搜索用时 15 毫秒
41.
Elisa Tran Annabelle Chow Takeshi Goda Amy Wong Kim Blakely Michelle Rocha Samira Taeb Van C. Hoang Stanley K. Liu Urban Emmenegger 《Biochemical and biophysical research communications》2013
ATG4B belongs to the autophagin family of cysteine proteases required for autophagy, an emerging target of cancer therapy. Developing pharmacological ATG4B inhibitors is a very active area of research. However, detailed studies on the role of ATG4B during anticancer therapy are lacking. By analyzing PC-3 and C4-2 prostate cancer cells overexpressing dominant negative ATG4BC74Ain vitro and in vivo, we show that the effects of ATG4BC74A are cell type, treatment, and context-dependent. ATG4BC74A expression can either amplify the effects of cytotoxic therapies or contribute to treatment resistance. Thus, the successful clinical application of ATG4B inhibitors will depend on finding predictive markers of response. 相似文献
42.
Nguyen The Tung To Dao Cuong Tran Manh Hung Jeong Hyung Lee Mi Hee Woo Jae Sue Choi Jaewang Kim Sung Ho Ryu Byung Sun Min 《Bioorganic & medicinal chemistry letters》2013,23(5):1428-1432
Four new lanostane triterpenes, butyl lucidenate P (1), butyl lucidenate D2 (2), butyl lucidenate E2 (3) and butyl lucidenate Q (4) along with 11 known compounds (5–15) were isolated from the fruiting bodies of Ganoderma lucidum. Their chemical structures were established mainly by 1D and 2D NMR techniques and mass spectrometry. Their anti-inflammatory activity was evaluated against LPS-induced NO production in macrophage RAW 264.7 cells. Compounds 1, 3, 4, 9, 10 and 15 showed inhibitory potency with IC50 values of 7.4, 6.4, 4.3, 9.4, 9.2 and 4.5 μM, respectively. Compounds 1, 3 and 15 dose-dependently reduced the LPS-induced iNOS expressions. Preincubation of cell with 1, 3 and 15 significantly suppressed LPS-induced expression of COX-2 protein. 相似文献
43.
Phuong-Thao Tran Van-Hai Hoang Shivaji A. Thorat Sung Eun Kim Jihyae Ann Yu Jin Chang Dong Woo Nam Hyundong Song Inhee Mook-Jung Jiyoun Lee Jeewoo Lee 《Bioorganic & medicinal chemistry》2013,21(13):3821-3830
In an effort to design inhibitors of human glutaminyl cyclase (QC), we have synthesized a library of N-aryl N-(5-methyl-1H-imidazol-1-yl)propyl thioureas and investigated the contribution of the aryl region of these compounds to their structure–activity relationships as cyclase inhibitors. Our design was guided by the proposed binding mode of the preferred substrate for the cyclase. In this series, compound 52 was identified as the most potent QC inhibitor with an IC50 value of 58 nM, which was two-fold more potent than the previously reported lead 2. Compound 52 is a most promising candidate for future evaluation to monitor its ability to reduce the formation of pGlu-Aβ and Aβ plaques in cells and transgenic animals. 相似文献
44.
Bo Li Ankita Umapathy Loi Uyen Tran Paul J. Donaldson Julie C. Lim 《Histochemistry and cell biology》2013,139(4):559-571
The aim of this study is to determine the contribution of the ciliary epithelium to glutathione (GSH) levels in the aqueous by mapping GSH metabolism and transport pathways in the rat ciliary body. Using a combination of molecular and immunohistochemical techniques, we screened and localised enzymes and transporters involved in GSH synthesis, uptake, efflux and degradation. Our findings indicate that both the pigmented epithelial (PE) and the non-pigmented epithelial (NPE) cell layers are capable of accumulating precursor amino acids for GSH synthesis, but only the NPE cells appear to be involved in the direct uptake of precursor amino acids from the stroma. The localisation of GSH efflux transporters to the PE cell and PE–NPE interface indicates that GSH and potentially GSH-S conjugates can be removed from the ciliary epithelium into the stroma, while the location of GSH efflux transporters to the basolateral membrane of the NPE indicates that these cells can mediate GSH secretion into the aqueous. GSH secreted by the ciliary into the aqueous would remain largely intact due to the absence of the GSH degradation enzymes γ-glutamyltranspeptidase (γ-GGT) labelling at the basolateral membrane of the NPE. Therefore, it appears that the ciliary epithelium contains the molecular machinery to mediate GSH secretion into the aqueous. 相似文献
45.
Bacterial cultures were enriched from sediments in Germany and Vietnam reductively dechlorinating hexachlorobenzene and the highly persistent 1,3,5-trichlorobenzene to monochlorobenzene. The main products of the reductive dechlorination of hexachlorobenzene were monochlorobenzene and dichlorobenzenes (1,2-; 1,3- and 1,4-dichlorobenzene) while no trichlorobenzenes accumulated. For the reductive dechlorination of 1,3,5-trichlorobenzene with the mixed culture from Vietnam sediment, 1,3- dichlorobenzene and monochlorobenzene were produced as intermediate and final end-product, respectively. The pattern of dechlorination did not change when the cultures were repeatedly exposed to oxygen over seven transfers demonstrating oxygen tolerance of the dechlorinating bacteria. However, reductive dechlorination of 1,3,5-trichlorobenzene was inhibited by vancomycin at a concentration of 5 mg L?1. Vancomycin delayed reductive dechlorination of hexachlorobenzene in mixed cultures by about 6 months. When repeatedly applied, vancomycin completely abolished the ability of the mixed culture to transform hexachlorobenzene. Sensitivity to vancomycin and insensitivity to brief exposure of oxygen indicates that the dechlorinating bacteria in the mixed cultures did not belong to the genus Dehalococcoides. 相似文献
46.
Chengrong Huang Juntao Kan Xu Liu Fenfen Ma Ba Hieu Tran Yunzeng Zou Shujun Wang Yi Zhun Zhu 《PloS one》2013,8(7)
Objective
Heart failure (HF) is one of the most serious diseases worldwide. S-propargyl-cysteine (SPRC), a novel modulator of endogenous hydrogen sulfide, is proved to be able to protect against acute myocardial ischemia. In order to produce more stable and sustainable hydrogen sulfide, we used controlled release formulation of SPRC (CR-SPRC) to elucidate possible cardioprotective effects on HF rats and investigate involved mechanisms on apoptosis and oxidation.Methods
Left coronary artery was occluded to induce HF model of rat. The survival rats were randomly divided into 7 groups after 24 hours and treated with drugs for 6 weeks. Echocardiographic indexes were recorded to determine cardiac function. TTC staining was performed to determine infarct size. Plasmatic level of hydrogen sulfide was detected by modified sulfide electrode. Activity of enzyme and expression of protein were determined by colorimetry and Western blot, respectively.Results
The cardioprotective effects of CR-SPRC on HF rats were confirmed by significant reduction of infarct size and improvement of cardiac function, with better effects compared to normal SPRC. CR-SPRC modulated antioxidant defenses by preserving levels of GSH, CAT and SOD and reducing CK leakage. In addition, CR-SPRC elevated ratio of Bcl-2/Bax and inhibited activity of caspases to protect against myocardial apoptosis. The cardioprotective effects of CR-SPRC were mediated by hydrogen sulfide.Conclusions
All experiment data indicated cardioprotective effects of CR-SPRC on HF rats. More importantly, CR-SPRC exerted better effects than normal SPRC in all respects, providing a new perspective on hydrogen sulfide-mediated drug therapy. 相似文献47.
48.
Phuong H. Nguyen Sunny S. Kim Tuan T. Nguyen Lan M. Tran Nemat Hajeebhoy Edward A. Frongillo Marie T. Ruel Rahul Rawat Purnima Menon 《PloS one》2016,11(3)
Adequate utilization of services is critical to maximize the impact of counselling on infant and young child feeding (IYCF), but little is known about factors affecting utilization. Our study examined supply- and demand-side factors associated with the utilization of IYCF counselling services in Viet Nam. We used survey data from mothers with children <2y (n = 1,008) and health staff (n = 60) from the evaluation of a program that embedded IYCF counseling into the existing government health system. The frequency of never users, one-time users, repeat users, and achievers of the recommended minimum number of visits at health facilities were 45.1%, 13.0%, 28.4% and 13.5%, respectively. Poisson regression showed that demand-generation strategies, especially invitation cards, were the key factors determining one-time use (Prevalence ratio, PR 3.0, 95% CI: 2.2–4.2), repeated use (PR 3.2, 95% CI: 2.4–4.2), and achievement of minimum visits (PR 5.5, 95% CI: 3.6–8.4). Higher maternal education was associated with higher utilization both for one-time and repeated use. Being a farmer, belonging to an ethnic minority, and having a wasted child were associated with greater likelihood of achieving the minimum recommended number of visits, whereas child stunting or illness were not. Distance to health center was a barrier to repeated visits. Among supply-side factors, good counselling skills (PR: 1.3–1.8) was the most important factor associated with any service use, whereas longer employment duration and greater work pressure of health center staff were associated with lower utilization. Population attributable risk estimations showed that an additional 25% of the population would have achieved the minimum number of visits if exposed to three demand-generation strategies, and further increased to 49% if the health staff had good counseling skills and low work pressure. Our study provides evidence that demand-generation strategies are essential to increase utilization of facility-based IYCF counselling services in Viet Nam, and may be relevant for increasing and sustaining use of nutrition services in similar contexts. 相似文献
49.
Van C. Tran 《Ethnic and racial studies》2016,39(13):2398-2403
ABSTRACTThis review engages with Jennifer Lee and Min Zhou’s The Asian American Achievement Paradox to consider how ethnic culture matters for social mobility among the immigrant second generation. It describes the strengths and contributions of the book, connects it to broader debates on culture, poverty, and mobility, and draws on my own research on the second generation in New York City. It highlights three additional cultural mechanisms that underlie the Chinese (or Asian) second-generation advantage: social class heterogeneity in the co-ethnic community, intergenerational support in the immigrant family, and the belief in achievements as redemption for parental sacrifice. While pointing out the similarities and differences between Los Angeles and New York, it also suggests possible applications of these cultural mechanisms in explaining second-generation achievements. 相似文献
50.
Tran Cuong Manh Van Pham Hai Nguyen Hien Thuy Nguyen Thuy Thi Vu Lam Dinh Do Tung Hoang 《Plasmonics (Norwell, Mass.)》2019,14(6):1587-1592
Plasmonics - Since the metamaterial perfect absorber (MPA) is composed of electromagnetic resonance structures, the main operational mechanism of the MPA is electromagnetic resonance. In this work,... 相似文献