全文获取类型
收费全文 | 1550篇 |
免费 | 153篇 |
国内免费 | 2篇 |
出版年
2023年 | 12篇 |
2022年 | 35篇 |
2021年 | 68篇 |
2020年 | 31篇 |
2019年 | 35篇 |
2018年 | 50篇 |
2017年 | 43篇 |
2016年 | 58篇 |
2015年 | 95篇 |
2014年 | 105篇 |
2013年 | 113篇 |
2012年 | 152篇 |
2011年 | 141篇 |
2010年 | 88篇 |
2009年 | 76篇 |
2008年 | 82篇 |
2007年 | 80篇 |
2006年 | 70篇 |
2005年 | 68篇 |
2004年 | 52篇 |
2003年 | 40篇 |
2002年 | 43篇 |
2001年 | 7篇 |
2000年 | 3篇 |
1999年 | 5篇 |
1998年 | 13篇 |
1997年 | 9篇 |
1994年 | 6篇 |
1993年 | 3篇 |
1992年 | 6篇 |
1988年 | 5篇 |
1987年 | 6篇 |
1984年 | 4篇 |
1982年 | 7篇 |
1981年 | 3篇 |
1980年 | 4篇 |
1979年 | 5篇 |
1978年 | 5篇 |
1977年 | 3篇 |
1976年 | 6篇 |
1974年 | 3篇 |
1973年 | 5篇 |
1972年 | 3篇 |
1965年 | 3篇 |
1964年 | 5篇 |
1961年 | 4篇 |
1960年 | 6篇 |
1930年 | 2篇 |
1902年 | 2篇 |
1899年 | 2篇 |
排序方式: 共有1705条查询结果,搜索用时 46 毫秒
121.
Chen CS Anaya JM Zhang S Spurgin J Chuang CY Xu C Miao AJ Chen EY Schwehr KA Jiang Y Quigg A Santschi PH Chin WC 《PloS one》2011,6(7):e21865
The unique properties of engineered nanoparticles (ENs) that make their industrial applications so attractive simultaneously raise questions regarding their environmental safety. ENs exhibit behaviors different from bulk materials with identical chemical compositions. Though the nanotoxicity of ENs has been studied intensively, their unintended environmental impacts remain largely unknown. Herein we report experimental results of EN interactions with exopolymeric substances (EPS) from three marine phytoplankton species: Amphora sp., Ankistrodesmus angustus and Phaeodactylum tricornutum. EPS are polysaccharide-rich anionic colloid polymers released by various microorganisms that can assemble into microgels, possibly by means of hydrophobic and ionic mechanisms. Polystyrene nanoparticles (23 nm) were used in our study as model ENs. The effects of ENs on EPS assembly were monitored with dynamic laser scattering (DLS). We found that ENs can induce significant acceleration in Amphora sp. EPS assembly; after 72 hours EN-EPS aggregation reached equilibrium, forming microscopic gels of ~4-6 μm in size. In contrast, ENs only cause moderate assembly kinetic acceleration for A. angustus and P. tricornutum EPS samples. Our results indicate that the effects of ENs on EPS assembly kinetics mainly depend on the hydrophobic interactions of ENs with EPS polymers. The cycling mechanism of EPS is complex. Nonetheless, the change of EPS assembly kinetics induced by ENs can be considered as one potential disturbance to the marine carbon cycle. 相似文献
122.
Roffman JL Nitenson AZ Agam Y Isom M Friedman JS Dyckman KA Brohawn DG Smoller JW Goff DC Manoach DS 《PloS one》2011,6(9):e25253
Background
Responding to errors is a critical first step in learning from mistakes, a process that is abnormal in schizophrenia. To gain insight into the neural and molecular mechanisms of error processing, we used functional MRI to examine effects of a genetic variant in methylenetetrahydrofolate reductase (MTHFR 677C>T, rs1801133) that increases risk for schizophrenia and that has been specifically associated with increased perseverative errors among patients. MTHFR is a key regulator of the intracellular one-carbon milieu, including DNA methylation, and each copy of the 677T allele reduces MTHFR activity by 35%.Methodology/Principal Findings
Using an antisaccade paradigm, we found that the 677T allele induces a dose-dependent blunting of dorsal anterior cingulate cortex (dACC) activation in response to errors, a pattern that was identical in healthy individuals and patients with schizophrenia. Further, the normal relationship between dACC activation and error rate was disrupted among carriers of the 677T allele.Conclusions/Significance
These findings implicate an epigenetic mechanism in the neural response to errors, and provide insight into normal cognitive variation through a schizophrenia risk gene. 相似文献123.
124.
Age-related differences in amplification of covalently closed circular DNA at early times after duck hepatitis B virus infection of ducks 总被引:1,自引:0,他引:1
下载免费PDF全文
![点击此处可从《Journal of virology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Inoculation of 3-day-old (3D) or 3-week-old (3W) ducklings with duck hepatitis B virus results in chronic or transient infection, respectively. We previously showed that rapid production of neutralizing antibody following inoculation of 3W ducklings prevents virus from spreading in the liver and leads to a transient infection (Y.-Y. Zhang and J. Summers, J. Virol. 78:1195-1201, 2004). In this study we further investigated early events of viral infection in both 3D and 3W ducks. We present evidence that a lower level of virus replication in the hepatocytes of 3W birds is an additional factor that probably favors transient infection. We suggest that lower virus replication is due to a less rapid covalently closed circular DNA amplification, leading to lower viremias and a slower spread of infection in the liver, and that the slower spread of infection in 3W ducks makes the infection more sensitive to interruption by the host immune responses. 相似文献
125.
Receptor-induced conformational changes in the SU subunit of the avian sarcoma/leukosis virus A envelope protein: implications for fusion activation
下载免费PDF全文
![点击此处可从《Journal of virology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
The avian sarcoma/leukosis virus (ASLV) is activated for fusion by a two-step mechanism. For ASLV subgroup A (ASLV-A), association with its receptor (Tva) at neutral pH converts virions to a form that can bind target membranes and, in some assays, induce the lipid-mixing stage of fusion. Low pH is necessary to complete the fusion reaction. ASLV-A env (EnvA) exists on the viral surface as a trimer of heterodimers consisting of receptor binding (SU-A) and fusion-mediating (TM-A) subunits. As the receptor binding and fusion-mediating functions reside in separate subunits, we hypothesize that SU-A and TM-A are conformationally coupled. To begin to understand the effect of the binding of a soluble 47-residue domain of the receptor (sTva) on this coupling and the subsequent function of low pH, we prepared recombinant proteins representing full-length SU-A and a nested set of deletion mutant proteins. Full-length SU-A binds sTva with high affinity, but even small deletions at either the N or the C terminus severely impair sTva binding. We have purified the full-length SU-A subunit and characterized its interactions with sTva and the subsequent effect of low pH on the complex. sTva binds SU-A with an apparent KD of 3 pM. Complex formation occludes hydrophobic surfaces and tryptophan residues and leads to a partial loss of alpha-helical structure in SU-A. Low pH does not alter the off rate for the complex, further alter the secondary structure of SU-A, or induce measurable changes in tryptophan environment. The implications of these findings for fusion are discussed. 相似文献
126.
127.
128.
129.
Aggregation of granulocyte-colony stimulating factor in vitro involves a conformationally altered monomeric state
下载免费PDF全文
![点击此处可从《Protein science : a publication of the Protein Society》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Raso SW Abel J Barnes JM Maloney KM Pipes G Treuheit MJ King J Brems DN 《Protein science : a publication of the Protein Society》2005,14(9):2246-2257
Aggregation of partially folded intermediates populated during protein folding processes has been described for many proteins. Likewise, partially unfolded chains, generated by perturbation of numerous proteins by heat or chemical denaturants, have also been shown to aggregate readily. However, the process of protein aggregation from native-state conditions is less well understood. Granulocyte-colony stimulating factor (G-CSF), a member of the four-helix bundle class of cytokines, is a therapeutically relevant protein involved in stimulating the growth and maturation of phagocytotic white blood cells. Under native-like conditions (37 degrees C [pH 7.0]), G-CSF shows a significant propensity to aggregate. Our data suggest that under these conditions, native G-CSF exists in equilibrium with an altered conformation, which is highly aggregation prone. This species is enriched in 1-2 M GdmCl, as determined by tryptophan fluorescence and increased aggregation kinetics. In particular, specific changes in Trp58 fluorescence report a local rearrangement in the large loop region between helices A and B. However, circular dichroism, reactivity toward cyanylation, and ANS binding demonstrate that this conformational change is subtle, having no substantial disruption of secondary and tertiary structure, reactivity of the free sulfhydryl at Cys17 or exposure of buried hydrophobic regions. There is no indication that this altered conformation is important to biological activity, making it an attractive target for rational protein stabilization. 相似文献
130.
Guillaume Lesage Jesse Shapiro Charles A Specht Anne-Marie Sdicu Patrice Ménard Shamiza Hussein Amy Hin Yan Tong Charles Boone Howard Bussey 《BMC genetics》2005,6(1):1-16