全文获取类型
收费全文 | 329篇 |
免费 | 41篇 |
出版年
2022年 | 3篇 |
2021年 | 6篇 |
2020年 | 2篇 |
2019年 | 5篇 |
2018年 | 5篇 |
2017年 | 3篇 |
2016年 | 8篇 |
2015年 | 13篇 |
2014年 | 11篇 |
2013年 | 16篇 |
2012年 | 29篇 |
2011年 | 19篇 |
2010年 | 17篇 |
2009年 | 14篇 |
2008年 | 21篇 |
2007年 | 18篇 |
2006年 | 16篇 |
2005年 | 14篇 |
2004年 | 24篇 |
2003年 | 18篇 |
2002年 | 10篇 |
2001年 | 9篇 |
2000年 | 4篇 |
1999年 | 4篇 |
1998年 | 4篇 |
1996年 | 2篇 |
1994年 | 2篇 |
1993年 | 4篇 |
1992年 | 3篇 |
1990年 | 5篇 |
1989年 | 2篇 |
1988年 | 7篇 |
1987年 | 2篇 |
1986年 | 1篇 |
1985年 | 1篇 |
1984年 | 4篇 |
1983年 | 5篇 |
1982年 | 5篇 |
1981年 | 1篇 |
1980年 | 6篇 |
1979年 | 2篇 |
1978年 | 2篇 |
1977年 | 4篇 |
1976年 | 4篇 |
1975年 | 2篇 |
1973年 | 1篇 |
1972年 | 1篇 |
1971年 | 4篇 |
1970年 | 2篇 |
1968年 | 1篇 |
排序方式: 共有370条查询结果,搜索用时 15 毫秒
121.
122.
PfSR1 controls alternative splicing and steady‐state RNA levels in Plasmodium falciparum through preferential recognition of specific RNA motifs
下载免费PDF全文
![点击此处可从《Molecular microbiology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Shiri Eshar Lindsey Altenhofen Alona Rabner Phil Ross Yair Fastman Yael Mandel‐Gutfreund Rotem Karni Manuel Llinás Ron Dzikowski 《Molecular microbiology》2015,96(6):1283-1297
Plasmodium species have evolved complex biology to adapt to different hosts and changing environments throughout their life cycle. Remarkably, these adaptations are achieved by a relatively small genome. One way by which the parasite expands its proteome is through alternative splicing (AS). We recently identified PfSR1 as a bona fide Ser/Arg‐rich (SR) protein that shuttles between the nucleus and cytoplasm and regulates AS in Plasmodium falciparum. Here we show that PfSR1 is localized adjacent to the Nuclear Pore Complex (NPC) clusters in the nucleus of early stage parasites. To identify the endogenous RNA targets of PfSR1, we adapted an inducible overexpression system for tagged PfSR1 and performed RNA immunoprecipitation followed by microarray analysis (RIP‐chip) to recover and identify the endogenous RNA targets that bind PfSR1. Bioinformatic analysis of these RNAs revealed common sequence motifs potentially recognized by PfSR1. RNA‐EMSAs show that PfSR1 preferentially binds RNA molecules containing these motifs. Interestingly, we find that PfSR1 not only regulates AS but also the steady‐state levels of mRNAs containing these motifs in vivo. 相似文献
123.
The response of Chlamydomonas reinhardtii to nitrogen deprivation: a systems biology analysis
下载免费PDF全文
![点击此处可从《The Plant journal : for cell and molecular biology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
124.
Robert J. Suhadolnik Paul W. Doetsch Yair Devash Earl E. Henderson Ramamurthy Charubala Wolfgang Pfleiderer 《Nucleosides, nucleotides & nucleic acids》2013,32(4):351-366
Abstract The effect of the 2′,5′-adenylate and cordycepin trimer cores on DNA and protein synthesis in human umbilical cord lymphocytes, lymphoblasts, peripheral blood lymphocytes and Epstein-Barr virus infected lymphocytes and their metabolism in tissue culture medium have been studied. [32P]Adenylate and [32P]- and [3H]cordycepin trimer cores were synthesized either enzymatically or chemically and added to cells in culture. The half-lives of the 2′,5′-A3 core and 2′,5′-3′dA3 core in tissue culture were 3 and 17 hr, respectively. Chromatographic analysis of the TCA-soluble extracts of the lymphocytes and lymphoblasts treated with 2′,5′-[3H]A3 showed that 0.25% of the 32P was identified as AMP, ADP, ATP and inorganic phosphate. By the more sensitive 2′,5′-p3A4[32P]pCp radiobinding assay, 2′,5′-A3 was detected in the TCA supernatants; however, there was no 5′-rephosphorylation. With the [3H]- and [32P]cordycepin trimer core, 0.55% and 1.3% of the radioactivity was in the TCA soluble extracts. Although there was no 5′-rephosphorylation as determined by radiobinding assay, the intact cordycepin trimer core was detected by tlc, radiobinding assay, and HPLC. Furthermore, in two experiments, the concentration of the cordycepin trimer core bound to or taken up by the lymphocytes was three-fold greater than the concentration in the medium. 2′,5′-A3 and 2′,5′-3′dA3 cores were both antimitogenic, but did not inhibit protein synthesis. 相似文献
125.
Yuan Xu Xinyu Fu Thomas D Sharkey Yair Shachar-Hill and Berkley J Walker 《Plant physiology》2021,186(1):297
Respiration in the light (RL) releases CO2 in photosynthesizing leaves and is a phenomenon that occurs independently from photorespiration. Since RL lowers net carbon fixation, understanding RL could help improve plant carbon-use efficiency and models of crop photosynthesis. Although RL was identified more than 75 years ago, its biochemical mechanisms remain unclear. To identify reactions contributing to RL, we mapped metabolic fluxes in photosynthesizing source leaves of the oilseed crop and model plant camelina (Camelina sativa). We performed a flux analysis using isotopic labeling patterns of central metabolites during 13CO2 labeling time course, gas exchange, and carbohydrate production rate experiments. To quantify the contributions of multiple potential CO2 sources with statistical and biological confidence, we increased the number of metabolites measured and reduced biological and technical heterogeneity by using single mature source leaves and quickly quenching metabolism by directly injecting liquid N2; we then compared the goodness-of-fit between these data and data from models with alternative metabolic network structures and constraints. Our analysis predicted that RL releases 5.2 μmol CO2 g−1 FW h−1 of CO2, which is relatively consistent with a value of 9.3 μmol CO2 g−1 FW h−1 measured by CO2 gas exchange. The results indicated that ≤10% of RL results from TCA cycle reactions, which are widely considered to dominate RL. Further analysis of the results indicated that oxidation of glucose-6-phosphate to pentose phosphate via 6-phosphogluconate (the G6P/OPP shunt) can account for >93% of CO2 released by RL. 相似文献
126.
Genome-based Flux Balance Analysis (FBA) and steady-state isotopic-labeling-based Metabolic Flux Analysis (MFA) are complimentary approaches to predicting and measuring the operation and regulation of metabolic networks. Here, genome-derived models of Escherichia coli (E. coli) metabolism were used for FBA and 13C-MFA analyses of aerobic and anaerobic growths of wild-type E. coli (K-12 MG1655) cells. Validated MFA flux maps reveal that the fraction of maintenance ATP consumption in total ATP production is about 14% higher under anaerobic (51.1%) than aerobic conditions (37.2%). FBA revealed that an increased ATP utilization is consumed by ATP synthase to secrete protons from fermentation. The TCA cycle is shown to be incomplete in aerobically growing cells and submaximal growth is due to limited oxidative phosphorylation. An FBA was successful in predicting product secretion rates in aerobic culture if both glucose and oxygen uptake measurement were constrained, but the most-frequently predicted values of internal fluxes yielded from sampling the feasible space differ substantially from MFA-derived fluxes. 相似文献
127.
Gupta RD Goldsmith M Ashani Y Simo Y Mullokandov G Bar H Ben-David M Leader H Margalit R Silman I Sussman JL Tawfik DS 《Nature chemical biology》2011,7(2):120-125
Organophosphate nerve agents are extremely lethal compounds. Rapid in vivo organophosphate clearance requires bioscavenging enzymes with catalytic efficiencies of >10(7) (M(-1) min(-1)). Although serum paraoxonase (PON1) is a leading candidate for such a treatment, it hydrolyzes the toxic S(p) isomers of G-agents with very slow rates. We improved PON1's catalytic efficiency by combining random and targeted mutagenesis with high-throughput screening using fluorogenic analogs in emulsion compartments. We thereby enhanced PON1's activity toward the coumarin analog of S(p)-cyclosarin by ~10(5)-fold. We also developed a direct screen for protection of acetylcholinesterase from inactivation by nerve agents and used it to isolate variants that degrade the toxic isomer of the coumarin analog and cyclosarin itself with k(cat)/K(M) ~ 10(7) M(-1) min(-1). We then demonstrated the in vivo prophylactic activity of an evolved variant. These evolved variants and the newly developed screens provide the basis for engineering PON1 for prophylaxis against other G-type agents. 相似文献
128.
Lesbats P Botbol Y Chevereau G Vaillant C Calmels C Arneodo A Andreola ML Lavigne M Parissi V 《PLoS pathogens》2011,7(2):e1001280
Establishment of stable HIV-1 infection requires the efficient integration of the retroviral genome into the host DNA. The molecular mechanism underlying the control of this process by the chromatin structure has not yet been elucidated. We show here that stably associated nucleosomes strongly inhibit in vitro two viral-end integration by decreasing the accessibility of DNA to integrase. Remodeling of the chromatinized template by the SWI/SNF complex, whose INI1 major component interacts with IN, restores and redirects the full-site integration into the stable nucleosome region. These effects are not observed after remodeling by other human remodeling factors such as SNF2H or BRG1 lacking the integrase binding protein INI1. This suggests that the restoration process depends on the direct interaction between IN and the whole SWI/SNF complex, supporting a functional coupling between the remodeling and integration complexes. Furthermore, in silico comparison between more than 40,000 non-redundant cellular integration sites selected from literature and nucleosome occupancy predictions also supports that HIV-1 integration is promoted in the genomic region of weaker intrinsic nucleosome density in the infected cell. Our data indicate that some chromatin structures can be refractory for integration and that coupling between nucleosome remodeling and HIV-1 integration is required to overcome this natural barrier. 相似文献
129.
Seifart Gomes C Izar B Pazan F Mohamed W Mraheil MA Mukherjee K Billion A Aharonowitz Y Chakraborty T Hain T 《PloS one》2011,6(9):e24965
Background
Pathogenic bacteria maintain a multifaceted apparatus to resist damage caused by external stimuli. As part of this, the universal stress protein A (UspA) and its homologues, initially discovered in Escherichia coli K-12 were shown to possess an important role in stress resistance and growth in several bacterial species.Methods and Findings
We conducted a study to assess the role of three homologous proteins containing the UspA domain in the facultative intracellular human pathogen Listeria monocytogenes under different stress conditions. The growth properties of three UspA deletion mutants (Δlmo0515, Δlmo1580 and Δlmo2673) were examined either following challenge with a sublethal concentration of hydrogen peroxide or under acidic conditions. We also examined their ability for intracellular survival within murine macrophages. Virulence and growth of usp mutants were further characterized in invertebrate and vertebrate infection models.Tolerance to acidic stress was clearly reduced in Δlmo1580 and Δlmo0515, while oxidative stress dramatically diminished growth in all mutants. Survival within macrophages was significantly decreased in Δlmo1580 and Δlmo2673 as compared to the wild-type strain. Viability of infected Galleria mellonella larvae was markedly higher when injected with Δlmo1580 or Δlmo2673 as compared to wild-type strain inoculation, indicating impaired virulence of bacteria lacking these usp genes. Finally, we observed severely restricted growth of all chromosomal deletion mutants in mice livers and spleens as compared to the load of wild-type bacteria following infection.Conclusion
This work provides distinct evidence that universal stress proteins are strongly involved in listerial stress response and survival under both in vitro and in vivo growth conditions. 相似文献130.
Vecsler M Ben Zeev B Nudelman I Anikster Y Simon AJ Amariglio N Rechavi G Baasov T Gak E 《PloS one》2011,6(6):e20733