全文获取类型
收费全文 | 2691篇 |
免费 | 290篇 |
国内免费 | 1篇 |
出版年
2023年 | 19篇 |
2022年 | 44篇 |
2021年 | 84篇 |
2020年 | 63篇 |
2019年 | 66篇 |
2018年 | 86篇 |
2017年 | 73篇 |
2016年 | 120篇 |
2015年 | 144篇 |
2014年 | 157篇 |
2013年 | 169篇 |
2012年 | 186篇 |
2011年 | 185篇 |
2010年 | 125篇 |
2009年 | 102篇 |
2008年 | 112篇 |
2007年 | 123篇 |
2006年 | 112篇 |
2005年 | 99篇 |
2004年 | 108篇 |
2003年 | 70篇 |
2002年 | 64篇 |
2001年 | 58篇 |
2000年 | 65篇 |
1999年 | 69篇 |
1998年 | 37篇 |
1997年 | 22篇 |
1996年 | 24篇 |
1995年 | 16篇 |
1994年 | 10篇 |
1993年 | 23篇 |
1992年 | 28篇 |
1991年 | 26篇 |
1990年 | 33篇 |
1989年 | 27篇 |
1988年 | 23篇 |
1987年 | 30篇 |
1986年 | 17篇 |
1985年 | 21篇 |
1984年 | 21篇 |
1983年 | 17篇 |
1982年 | 8篇 |
1980年 | 6篇 |
1979年 | 7篇 |
1978年 | 10篇 |
1976年 | 6篇 |
1975年 | 12篇 |
1971年 | 7篇 |
1970年 | 6篇 |
1969年 | 9篇 |
排序方式: 共有2982条查询结果,搜索用时 62 毫秒
121.
Fellippo Ramos Verri Ronaldo Silva Cruz Victor Eduardo de Souza Batista Daniel Augusto de Faria Almeida Ana Caroline Gonçales Verri Cleidiel Aparecido de Araújo Lemos 《Computer methods in biomechanics and biomedical engineering》2016,19(15):1665-1672
The aim of this study was to assess stress/strain of different implant modeling simplifications by 3D-FEA. Three variation of external hexagon implant (Ø3.75?×?10 mm) supporting one molar crown were simulated: A (no threads); B (slightly threads simplification); C (original design). 200 N (axial) and 100 N (oblique) were applied. Cortical bone was evaluated by maximum principal stress and microstrain qualitatively and quantitatively (ANOVA and Tukey post hoc (p < 0.05)). Higher stress levels (p < 0.05) were observed in model A. Models B and C presented similar stress transmission. It was possible to conclude that slightly simplification should be used for studies evaluating stress transferring for bone tissue. 相似文献
122.
João Paulo Oliveira Corrêa Camilo Elber Vital Marcos Vinícius Marques Pinheiro Diego Silva Batista Cleber Witt Saldanha Ana Cláudia Ferreira da Cruz Marcela Morato Notini Débora Márcia Silva Freitas Fábio Murilo DaMatta Wagner Campos Otoni 《In vitro cellular & developmental biology. Plant》2016,52(1):45-55
123.
Jessica Tauany Andrade Geisa Fantini de Figueiredo Luisa Ferreira Cruz Sarah Eliza de Morais Carla Daiane Ferreira Souza Flávia Carmo Horta Pinto Jaqueline Maria Siqueira Ferreira Marcelo Gonzaga de Freitas Araújo 《Revista iberoamericana de micología》2019,36(4):192-199
BackgroundCandida albicans is the main agent that causes vulvovaginal candidiasis. Resistance among isolates to azole antifungal agents has been reported.AimsDue to the well-known antifungal potential of curcumin, the purpose of this work was to evaluate the in vitro anticandidal activity of curcumin and its effect in the treatment of experimental vulvovaginal candidiasis.MethodsThe anticandidal activity of curcumin was investigated against eight Candida strains by the broth microdilution assay, and its mechanism of action was evaluated by testing the binding to ergosterol. Then, the effect of curcumin in the treatment of vulvovaginal candidiasis was evaluated in an immunosuppressed, estrogen treated rat model.ResultsCurcumin showed minimum inhibitory concentration values of 125–1000 μg/ml, and the best result was observed against Candida glabrata. The compound was shown to be able to bind to the ergosterol present in the membrane, event that may be the mechanism of action. In addition, in the in vivo model of vulvovaginal candidiasis with C. albicans, treatments reduced the vaginal fungal burden in infected rats after seven days of treatment with different doses.ConclusionsCurcumin could be considered a promising effective antifungal agent in the treatment of vulvovaginal candidiasis. 相似文献
124.
Dhimant Desai Matthew Lauver Alexandria Ostman Linda Cruz Kevin Ferguson Ge Jin Brianne Roper Daniel Brosius Aron Lukacher Shantu Amin Nick Buchkovich 《Bioorganic & medicinal chemistry》2019,27(9):1795-1803
Opportunistic viruses are a major problem for immunosuppressed individuals, particularly following organ or stem cell transplantation. Current treatments are non-existent or suffer from problems such as high toxicity or development of resistant strains. We previously published that a trafficking inhibitor that targets a host protein greatly reduces the replication of human cytomegalovirus. This inhibitor was also shown to be moderately effective against polyomaviruses, another family of opportunistic viruses. We have developed a panel of analogues for this inhibitor and have shown that these analogues maintain their high efficacy against HCMV, while substantially lowering the concentration required to inhibit polyomavirus replication. By targeting a host protein these compounds are able to inhibit the replication of two very different viruses. These observations open up the possibility of pan-viral inhibitors for immunosuppressed individuals that are effective against multiple, diverse opportunistic viruses. 相似文献
125.
Edward R. Cruz Hung Nguyen Tin Nguyen Ian S. Wallace 《The Plant journal : for cell and molecular biology》2019,99(5):1003-1013
Post‐translational modifications (PTMs) are critical regulators of protein function, and nearly 200 different types of PTM have been identified. Advances in high‐resolution mass spectrometry have led to the identification of an unprecedented number of PTM sites in numerous organisms, potentially facilitating a more complete understanding of how PTMs regulate cellular behavior. While databases have been created to house the resulting data, most of these resources focus on individual types of PTM, do not consider quantitative PTM analyses or do not provide tools for the visualization and analysis of PTM data. Here, we describe the Functional Analysis Tools for Post‐Translational Modifications (FAT‐PTM) database ( https://bioinformatics.cse.unr.edu/fat-ptm/ ), which currently supports eight different types of PTM and over 49 000 PTM sites identified in large‐scale proteomic surveys of the model organism Arabidopsis thaliana. The FAT‐PTM database currently supports tools to visualize protein‐centric PTM networks, quantitative phosphorylation site data from over 10 different quantitative phosphoproteomic studies, PTM information displayed in protein‐centric metabolic pathways and groups of proteins that are co‐modified by multiple PTMs. Overall, the FAT‐PTM database provides users with a robust platform to share and visualize experimentally supported PTM data, develop hypotheses related to target proteins or identify emergent patterns in PTM data for signaling and metabolic pathways. 相似文献
126.
Jos C. E. Serrano Juan Antonio Baena‐Fustegueras Meritxell Martin‐Gari Helene Rassendren Anna Cassanye Alba Naudí Carolina Lpez‐Cano Enric Snchez María Cruz de la Fuente‐Jurez Fernando Herrerías Gonzlez Jorge J. Olsina Kissler Albert Lecube Manuel Portero‐Otín 《Obesity (Silver Spring, Md.)》2019,27(7):1133-1140
127.
Role of electrostatic interactions in amyloid beta-protein (A beta) oligomer formation: a discrete molecular dynamics study
下载免费PDF全文
![点击此处可从《Biophysical journal》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Pathological folding and oligomer formation of the amyloid beta-protein (A beta) are widely perceived as central to Alzheimer's disease. Experimental approaches to study A beta self-assembly provide limited information because most relevant aggregates are quasi-stable and inhomogeneous. We apply a discrete molecular dynamics approach combined with a four-bead protein model to study oligomer formation of A beta. We address the differences between the two most common A beta alloforms, A beta 40 and A beta 42, which oligomerize differently in vitro. Our previous study showed that, despite simplifications, our discrete molecular dynamics approach accounts for the experimentally observed differences between A beta 40 and A beta 42 and yields structural predictions amenable to in vitro testing. Here we study how the presence of electrostatic interactions (EIs) between pairs of charged amino acids affects A beta 40 and A beta 42 oligomer formation. Our results indicate that EIs promote formation of larger oligomers in both A beta 40 and A beta 42. Both A beta 40 and A beta 42 display a peak at trimers/tetramers, but A beta 42 displays additional peaks at nonamers and tetradecamers. EIs thus shift the oligomer size distributions to larger oligomers. Nonetheless, the A beta 40 size distribution remains unimodal, whereas the A beta 42 distribution is trimodal, as observed experimentally. We show that structural differences between A beta 40 and A beta 42 that already appear in the monomer folding, are not affected by EIs. A beta 42 folded structure is characterized by a turn in the C-terminus that is not present in A beta 40. We show that the same C-terminal region is also responsible for the strongest intermolecular contacts in A beta 42 pentamers and larger oligomers. Our results suggest that this C-terminal region plays a key role in the formation of A beta 42 oligomers and the relative importance of this region increases in the presence of EIs. These results suggest that inhibitors targeting the C-terminal region of A beta 42 oligomers may be able to prevent oligomer formation or structurally modify the assemblies to reduce their toxicity. 相似文献
128.
Goudar CT Matanguihan R Long E Cruz C Zhang C Piret JM Konstantinov KB 《Biotechnology and bioengineering》2007,96(6):1107-1117
High-density perfusion cultivation of mammalian cells can result in elevated bioreactor CO(2) partial pressure (pCO(2)), a condition that can negatively influence growth, metabolism, productivity, and protein glycosylation. For BHK cells in a perfusion culture at 20 x 10(6) cells/mL, the bioreactor pCO(2) exceeded 225 mm Hg with approximate contributions of 25% from cellular respiration, 35% from medium NaHCO(3), and 40% from NaHCO(3) added for pH control. Recognizing the limitations to the practicality of gas sparging for CO(2) removal in perfusion systems, a strategy based on CO(2) reduction at the source was investigated. The NaHCO(3) in the medium was replaced with a MOPS-Histidine buffer, while Na(2)CO(3) replaced NaHCO(3) for pH control. These changes resulted in 63-70% pCO(2) reductions in multiple 15 L perfusion bioreactors, and were reproducible at the manufacturing-scale. Bioreactor pCO(2) values after these modifications were in the 68-85 mm Hg range, pCO(2) reductions consistent with those theoretically expected. Low bioreactor pCO(2) was accompanied by both 68-123% increased growth rates and 58-92% increased specific productivity. Bioreactor pCO(2) reduction and the resulting positive implications for cell growth and productivity were brought about by process changes that were readily implemented and robust. This philosophy of pCO(2) reduction at the source through medium and base modification should be readily applicable to large-scale fed-batch cultivation of mammalian cells. 相似文献
129.
Tato I Matilla I Arechaga I Zunzunegui S de la Cruz F Cabezon E 《The Journal of biological chemistry》2007,282(35):25569-25576
Conjugative systems contain an essential integral membrane protein involved in DNA transport called the Type IV coupling protein (T4CP). The T4CP of conjugative plasmid R388 is TrwB, a DNA-dependent ATPase. Biochemical and structural data suggest that TrwB uses energy released from ATP hydrolysis to pump DNA through its central channel by a mechanism similar to that used by F1-ATPase or ring helicases. For DNA transport, TrwB couples the relaxosome (a DNA-protein complex) to the secretion channel. In this work we show that TrwA, a tetrameric oriT DNA-binding protein and a component of the R388 relaxosome, stimulates TrwBDeltaN70 ATPase activity, revealing a specific interaction between the two proteins. This interaction occurs via the TrwA C-terminal domain. A 68-kDa complex between TrwBDeltaN70 and TrwA C-terminal domain was observed by gel filtration chromatography, consistent with a 1:1 stoichiometry. Additionally, electron microscopy revealed the formation of oligomeric TrwB complexes in the presence, but not in the absence, of TrwA protein. TrwBDeltaN70 ATPase activity in the presence of TrwA was further enhanced by DNA. Interestingly, maximal ATPase rates were achieved with TrwA and different types of dsDNA substrates. This is consistent with a role of TrwA in facilitating the interaction between TrwB and DNA. Our findings provide a new insight into the mechanism by which TrwB recruits the relaxosome for DNA transport. The process resembles the mechanism used by other DNA-dependent molecular motors, such as the RuvA/RuvB system, to be targeted to the DNA followed by hexamer assembly. 相似文献
130.