全文获取类型
收费全文 | 1508篇 |
免费 | 124篇 |
出版年
2023年 | 26篇 |
2022年 | 25篇 |
2021年 | 62篇 |
2020年 | 35篇 |
2019年 | 36篇 |
2018年 | 44篇 |
2017年 | 48篇 |
2016年 | 48篇 |
2015年 | 97篇 |
2014年 | 85篇 |
2013年 | 114篇 |
2012年 | 128篇 |
2011年 | 118篇 |
2010年 | 71篇 |
2009年 | 64篇 |
2008年 | 73篇 |
2007年 | 69篇 |
2006年 | 54篇 |
2005年 | 49篇 |
2004年 | 45篇 |
2003年 | 48篇 |
2002年 | 50篇 |
2001年 | 23篇 |
2000年 | 20篇 |
1999年 | 22篇 |
1997年 | 12篇 |
1996年 | 5篇 |
1995年 | 8篇 |
1994年 | 11篇 |
1993年 | 3篇 |
1992年 | 13篇 |
1991年 | 15篇 |
1990年 | 14篇 |
1989年 | 6篇 |
1988年 | 11篇 |
1987年 | 8篇 |
1986年 | 8篇 |
1985年 | 7篇 |
1984年 | 5篇 |
1983年 | 8篇 |
1982年 | 5篇 |
1981年 | 3篇 |
1979年 | 7篇 |
1978年 | 4篇 |
1977年 | 4篇 |
1976年 | 4篇 |
1975年 | 3篇 |
1974年 | 2篇 |
1973年 | 3篇 |
1972年 | 2篇 |
排序方式: 共有1632条查询结果,搜索用时 15 毫秒
71.
Matthew A. D. Brodie Michael Psarakis Phu Hoang 《Computer methods in biomechanics and biomedical engineering》2016,19(12):1339-1346
Accelerometers are incorporated into many consumer devices providing new ways to monitor gait, mobility, and fall risk. However, many health benefits have not been realised because of issues with data quality that results from gravitational ‘cross-talk’ when the wearable device is tilted. Here we present an adaptive filter designed to improve the quality of accelerometer data prior to measuring dynamic pelvic sway patterns during a six minute walk test in people with and without Multiple Sclerosis (MS). Optical motion capture was used as the gold standard. Improved wearable device accuracy (≤4.4% NRMSE) was achieved using gyroscopic corrections and scaling filter thresholds by step frequency. The people with MS presented significantly greater pelvis sway range to compensate for their lower limb weaknesses and joint contractures. The visualisation of asymmetric pelvic sway in people with MS illustrates the potential to better understand their mobility impairments for reducing fall risk. 相似文献
72.
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
73.
Mckayla Stevens Sanofar Abdeen Nilshad Salim Anne-Marie Ray Alex Washburn Siddhi Chitre Jared Sivinski Yangshin Park Quyen Q. Hoang Eli Chapman Steven M. Johnson 《Bioorganic & medicinal chemistry letters》2019,29(9):1106-1112
All living organisms contain a unique class of molecular chaperones called 60?kDa heat shock proteins (HSP60 – also known as GroEL in bacteria). While some organisms contain more than one HSP60 or GroEL isoform, at least one isoform has always proven to be essential. Because of this, we have been investigating targeting HSP60 and GroEL chaperonin systems as an antibiotic strategy. Our initial studies focused on applying this antibiotic strategy for treating African sleeping sickness (caused by Trypanosoma brucei parasites) and drug-resistant bacterial infections (in particular Methicillin-resistant Staphylococcus aureus – MRSA). Intriguingly, during our studies we found that three known antibiotics – suramin, closantel, and rafoxanide – were potent inhibitors of bacterial GroEL and human HSP60 chaperonin systems. These findings prompted us to explore what other approved drugs, natural products, and known bioactive molecules might also inhibit HSP60 and GroEL chaperonin systems. Initial high-throughput screening of 3680 approved drugs, natural products, and known bioactives identified 161 hit inhibitors of the Escherichia coli GroEL chaperonin system (4.3% hit rate). From a purchased subset of 60 hits, 29 compounds (48%) re-confirmed as selective GroEL inhibitors in our assays, all of which were nearly equipotent against human HSP60. These findings illuminate the notion that targeting chaperonin systems might be a more common occurrence than we previously appreciated. Future studies are needed to determine if the in vivo modes of action of these approved drugs, natural products, and known bioactive molecules are related to GroEL and HSP60 inhibition. 相似文献
74.
Ho Shin Kim Van-Hai Hoang Mannkyu Hong Kyung Chul Kim Jihyae Ann Cong-Truong Nguyen Ji Hae Seo Hoon Choi Jun Yong Kim Kyu-Won Kim Woong Sub Byun Sangkook Lee Seungbeom Lee Young-Ger Suh Jie Chen Hyun-Ju Park Tae-Min Cho Ji Young Kim Jeewoo Lee 《Bioorganic & medicinal chemistry》2019,27(7):1370-1381
On the basis of deguelin, a series of the B,C-ring truncated surrogates with N-substituted amide linkers were investigated as HSP90 inhibitors. The structure activity relationship of the template was studied by incorporating various substitutions on the nitrogen of the amide linker and examining their HIF-1α inhibition. Among them, compound 57 showed potent HIF-1α inhibition and cytotoxicity in triple-negative breast cancer lines in a dose-dependent manner. Compound 57 downregulated expression and phosphorylation of major client proteins of HSP90 including AKT, ERK and STAT3, indicating that its antitumor activity was derived from the inhibition of HSP90 function. The molecular modeling of 57 demonstrated that 57 bound well to the C-terminal ATP-binding pocket in the open conformation of the hHSP90 homodimer with hydrogen bonding and pi-cation interactions. Overall, compound 57 is a potential antitumor agent for triple-negative breast cancer as a HSP90 C-terminal inhibitor. 相似文献
75.
76.
Dinh T. Lam Bui C. Buu Nguyen T. Lang Kinya Toriyama Ikuo Nakamura Ryuji Ishikawa 《Ecology and evolution》2019,9(5):2964-2977
Oryza rufipogon Griff. is a perennial species of wild rice widely distributed along the channels and rivers of the Mekong Delta, Vietnam. This study attempted to find centers of diversity among wild rice populations in this area and their inter‐relationships. The highest genetic diversity was found in the Dong Thap population and the lowest in the Can Tho population. Maternal diversity evaluated using chloroplast INDELs detected ten plastid types, five of which were novel relative to other Asian countries. The mitochondrial genome suggested two unique deletions. One 699‐bp deletion via short tandem repeats was accompanied by another deletion including orf153. All accessions carrying the mitochondrial type were found in a particular plastid type. This unique maternal lineage was confined to specific channels where it showed vigorous vegetative growth in comparison to upstream areas where various maternal lineages and maximum genetic diversity occurred. This area along the Mekong Delta is a center of not only nuclear but also maternal diversity. 相似文献
77.
78.
Hamdane D Vasseur-Godbillon C Baudin-Creuza V Hoa GH Marden MC 《The Journal of biological chemistry》2007,282(9):6398-6404
Using high hydrostatic pressure or hydrogen peroxide as perturbing agents, we demonstrate a protective effect of the chaperone AHSP for the alpha-chains of Hb. High pressure induces an irreversible aggregation of the ferrous deoxy alpha-chains, whereas the AHSP/alpha-Hb complex shows reversible hexacoordination of the alpha-Hb without protein aggregation. Upon pressure release, the relaxation kinetics of the transition from the hexacoordinated to pentacoordinated form of alpha-Hb in the presence of AHSP exhibit a biphasic shape. High pressure did not induce dissociation of alpha-Hb from its chaperone, as evidenced by the ligand binding kinetics that show a unique rate for the AHSP/alpha-Hb complex. For both free alpha-Hb and the AHSP/alpha-Hb complex, the bimolecular rate constant of CO binding (k(CO)(on)) versus pressure exhibits a bell shape, attributed to the transition of the rate-determining step from the chemical barrier to the migration of CO within the protein matrix. These results reveal a plasticity of the alpha-Hb active site in the presence of the chaperone and indicate that the AHSP was still active at 300 MPa. The ferric state of the AHSP/alpha-Hb complex shows hexacoordination even at atmospheric pressures, indicating a His-Fe-His binding scheme as previously observed in neuroglobin and cytoglobin. The reaction with hydrogen peroxide of ferric alpha-Hb within the complex also demonstrates a protection against aggregation. 相似文献
79.
Dinh M Grunberger D Ho H Tsing SY Shaw D Lee S Barnett J Hill RJ Swinney DC Bradshaw JM 《The Journal of biological chemistry》2007,282(12):8768-8776
Bruton's tyrosine kinase (BTK) is a member of the Tec non-receptor tyrosine kinase family that is involved in regulating B cell proliferation. To better understand the enzymatic mechanism of the Tec family of kinases, the kinetics of BTK substrate phosphorylation were characterized using a radioactive enzyme assay. We first examined whether autophosphorylation regulates BTK activity. Western blotting with a phosphospecific antibody revealed that BTK rapidly autophosphorylates at Tyr(551) within its activation loop in vitro. Examination of a Y551F BTK mutant indicated that phosphorylation of Tyr(551) causes a 10-fold increase in BTK activity. We then proceeded to characterize the steady state kinetic mechanism of BTK. Varying the concentrations of ATP and S1 peptide (biotin-Aca-AAAEEIY-GEI-NH2) revealed that BTK employs a ternary complex mechanism with KmATP = 84 +/- 20 microM and KmS1 = 37 +/- 8 microM. Inhibition studies were also performed to examine the order of substrate binding. The inhibitors ADP and staurosporine were both found to be competitive with ATP and non-competitive with S1, indicating binding of ATP and S1 to BTK is either random or ordered with ATP binding first. Negative cooperativity was also found between the S1 and ATP binding sites. Unlike ATP site inhibitors, substrate analog inhibitors did not inhibit BTK at concentrations less than 1 mm, suggesting that BTK may employ a "substrate clamping" type of kinetic mechanism whereby the substrate Kd is weaker than Km. This investigation of BTK provides the first detailed kinetic characterization of a Tec family kinase. 相似文献
80.
Nguyen Mai Cao Hoang Phuong Lan Pham Van Huan Nguyen Huu Thong Duy-Hung Nguyen Nguyen Duc Trung Kien Chu Manh Nhuong Cao Xuan Thang Vuong-Hung Pham 《Luminescence》2022,37(4):577-587
A series of Mn2+-doped zinc germinate ZGO:xMn2+ (x = 0–0.05) nanorods was synthesized successfully using a hydrothermal method. XRD revealed that crystal phases of the ZGO:xMn2+ were rhombohedral and in the R-3 space group. The Williamson–Hall equation was also used to explain the strain, nanocrystalline size, and stacking fault. Green LEDs were successfully fabricated by coating ZGO:Mn2+ nanorods onto UV-LED chips. For high color purity, CIE of the fabricated green LEDs were (0.2404, 0.5428), which made this material a promising candidate for fabrication of UV-based green LEDs. 相似文献