全文获取类型
收费全文 | 2705篇 |
免费 | 129篇 |
专业分类
2834篇 |
出版年
2024年 | 1篇 |
2023年 | 18篇 |
2022年 | 32篇 |
2021年 | 64篇 |
2020年 | 55篇 |
2019年 | 69篇 |
2018年 | 90篇 |
2017年 | 69篇 |
2016年 | 119篇 |
2015年 | 145篇 |
2014年 | 154篇 |
2013年 | 206篇 |
2012年 | 263篇 |
2011年 | 238篇 |
2010年 | 135篇 |
2009年 | 119篇 |
2008年 | 182篇 |
2007年 | 210篇 |
2006年 | 154篇 |
2005年 | 167篇 |
2004年 | 109篇 |
2003年 | 95篇 |
2002年 | 81篇 |
2001年 | 12篇 |
2000年 | 5篇 |
1999年 | 7篇 |
1998年 | 14篇 |
1997年 | 4篇 |
1996年 | 3篇 |
1995年 | 1篇 |
1994年 | 1篇 |
1993年 | 1篇 |
1991年 | 4篇 |
1989年 | 3篇 |
1988年 | 1篇 |
1986年 | 1篇 |
1985年 | 1篇 |
1984年 | 1篇 |
排序方式: 共有2834条查询结果,搜索用时 0 毫秒
91.
92.
Paul F. Agris Marie T. Marchbank Winnell Newman Richard Guenther Phyllis Ingram Jacinda Swallow Piotr Mucha Agnieszka Szyk Piotr Rekowski Elena Peletskaya Susan L. Deutscher 《The protein journal》1999,18(4):425-435
Peptides that bind either U1 small nuclear RNA (U1 snRNA) or the anticodon stem and loop of yeast tRNAPhe (tRNA AC Phe ) were selected from a random-sequence, 15-amino acid bacteriophage display library. An experimental system, including an affinity selection method, was designed to identify primary RNA-binding peptide sequences without bias to known amino acid sequences and without incorporating nonspecific binding of the anionic RNA backbone. Nitrocellulose binding assays were used to evaluate the binding of RNA by peptide-displaying bacteriophage. Amino acid sequences of RNA-binding bacteriophage were determined from the foreign insert DNA sequences, and peptides corresponding to the RNA-binding bacteriophage inserts were chemically synthesized. Peptide affinities for the RNAs (K d ? 0.1–5.0 μM) were analyzed successfully using fluorescence and circular dichroism spectroscopies. These methodologies demonstrate the feasibility of rapidly identifying, isolating, and initiating the analyses of small peptides that bind to RNAs in an effort to define better the chemistry, structure, and function of protein–RNA complexes. 相似文献
93.
94.
Effects of anesthetics on systemic hemodynamics in mice 总被引:1,自引:0,他引:1
Janssen BJ De Celle T Debets JJ Brouns AE Callahan MF Smith TL 《American journal of physiology. Heart and circulatory physiology》2004,287(4):H1618-H1624
The aim of this study was to compare the systemic hemodynamic effects of four commonly used anesthetic regimens in mice that were chronically instrumented for direct and continuous measurements of cardiac output (CO). Mice (CD-1, Swiss, and C57BL6 strains) were instrumented with a transit-time flow probe placed around the ascending aorta for CO measurement. An arterial catheter was inserted into the aorta 4 or 5 days later for blood pressure measurements. After full recovery, hemodynamic parameters including stroke volume, heart rate, CO, mean arterial pressure (MAP), and total peripheral resistance were measured with animals in the conscious state. General anesthesia was then induced in these mice using isoflurane (Iso), urethane, pentobarbital sodium, or ketamine-xylazine (K-X). The doses and routes of administration of these agents were given as required for general surgical procedures in these animals. Compared with the values obtained for animals in the conscious resting state, MAP and CO decreased during all anesthetic interventions, and hemodynamic effects were smallest for Iso (MAP, -24 +/- 3%; CO, -5 +/- 7%; n = 15 mice) and greatest for K-X (MAP, -51 +/- 6%; CO, -37 +/- 9%; n = 8 mice), respectively. The hemodynamic effects of K-X were fully antagonized by administration of the alpha(2)-receptor antagonist atipamezole (n = 8 mice). These results indicate that the anesthetic Iso has fewer systemic hemodynamic effects in mice than the nonvolatile anesthetics. 相似文献
95.
A number of in planta transformation protocols that avoid long culture under sterile conditions were developed for Arabidopsis thaliana. The most widely used methods are based on vacuum infiltration and floral dip. These methods were adapted for transformation
of other species as well. Successful in planta transformations of alfalfa, radish, pakchoi and petunia were reported recently. In this short review we present several modified
procedures originally developed for Arabidopsis thaliana and in some cases adapted to other species. We emphasize the crucial parameters involved in in planta transformation. We also describe here the studies attempting to shed light on the mechanisms and estimating the cellular
target of transformation, which may help in transforming new plant species. 相似文献
96.
Kwiecień RA Rostkowski M Dybała-Defratyka A Paneth P 《Journal of inorganic biochemistry》2004,98(6):1078-1086
Several semiempirical methods (MNDO-d, PM3tm, PM3-d, PM5, PM6, and AM1-d) have been tested against experimental data and density functional theory (DFT) results in search for the best methods that can be used for quantum-mechanical-molecular mechanics (QM/MM) modeling of corrinoid systems of vitamin B(12) co-factor. It has been found that the PM6 parametrization in its present form gives results closest to hybrid DFT calculations that are most widely used thus far. In comparison with pure DFT and experimental data the best agreement is obtained for PM3tm parametrization, while PM6 yields slightly worse results. AM1-d yields bad geometry of the corrin moiety. The worst performance was observed for MNDO-d, which has severe problem with position and orientation of the alpha-ligands. 相似文献
97.
Gralak MA Bertrandt J Klos A Stryczek AB Piastowska AW Morka A Debski B 《Biological trace element research》2004,98(1):85-93
The aim of the present study was to investigate the influence of nutritional deficiency and dietary addition of vitamins (B2, B6, and folate) on hepatic concentration of zinc and copper in rats. The experiment was performed on 260 growing male Wistar
rats divided into 13 groups. Animals of 11 groups were fed isocaloric diets (14.7 MJ/kg) in which the 20% of energy was derived
from protein. Another two groups of rats were offered diets with 9% or 4.5% of energy originating from protein. Animals of
both mentioned groups and of the control group (20% of energy from protein) were offered diets ad libitum. The other 10 groups were offered 50% and 30% of the amount consumed in the control group. Eight groups, from those 10 restricted
ones, were differentiated by dietary addition of vitamins B2 and B6 and folate (300% addition). Restricted feed intake did not affect the liver zinc concentration but significantly increased
the copper concentration. The addition of vitamin B6 decreased the liver Zn concentration. The highest liver Cu concentration was noted in rats offered restricted diets to only
30% of intake in the control group and high in vitamin B2 and in rats supplemented with all of studied vitamins together. It suggests that vitamin B2 had the strongest impact on liver Cu concentration in rats fed restricted diets. 相似文献
98.
Essential role of Mia40 in import and assembly of mitochondrial intermembrane space proteins 总被引:11,自引:0,他引:11
Chacinska A Pfannschmidt S Wiedemann N Kozjak V Sanjuán Szklarz LK Schulze-Specking A Truscott KN Guiard B Meisinger C Pfanner N 《The EMBO journal》2004,23(19):3735-3746
Mitochondria import nuclear-encoded precursor proteins to four different subcompartments. Specific import machineries have been identified that direct the precursor proteins to the mitochondrial outer membrane, inner membrane or matrix, respectively. However, a machinery dedicated to the import of mitochondrial intermembrane space (IMS) proteins has not been found so far. We have identified the essential IMS protein Mia40 (encoded by the Saccharomyces cerevisiae open reading frame YKL195w). Mitochondria with a mutant form of Mia40 are selectively inhibited in the import of several small IMS proteins, including the essential proteins Tim9 and Tim10. The import of proteins to the other mitochondrial subcompartments does not depend on functional Mia40. The binding of small Tim proteins to Mia40 is crucial for their transport across the outer membrane and represents an initial step in their assembly into IMS complexes. We conclude that Mia40 is a central component of the protein import and assembly machinery of the mitochondrial IMS. 相似文献
99.
Papasavvas E Kostman JR Mounzer K Grant RM Gross R Gallo C Azzoni L Foulkes A Thiel B Pistilli M Mackiewicz A Shull J Montaner LJ 《PLoS medicine》2004,1(3):e64
Background
Approaches to limiting exposure to antiretroviral therapy (ART) drugs are an active area of HIV therapy research. Here we present longitudinal follow-up of a randomized, open-label, single-center study of the immune, viral, and safety outcomes of structured therapy interruptions (TIs) in patients with chronically suppressed HIV-1 infection as compared to equal follow-up of patients on continuous therapy and including a final therapy interruption in both arms.Methods and Findings
Forty-two chronically HIV-infected patients on suppressive ART with CD4 counts higher than 400 were randomized 1:1 to either (1) three successive fixed TIs of 2, 4, and 6 wk, with intervening resumption of therapy with resuppression for 4 wk before subsequent interruption, or (2) 40 wk of continuous therapy, with a final open-ended TI in both treatment groups. Main outcome was analysis of the time to viral rebound (>5,000 copies/ml) during the open-ended TI. Secondary outcomes included study-defined safety criteria, viral resistance, therapy failure, and retention of immune reconstitution.There was no difference between the groups in time to viral rebound during the open-ended TI (continuous therapy/single TI, median [interquartile range] = 4 [1–8] wk, n = 21; repeated TI, median [interquartile range] = 5 [4–8] wk, n = 21; p = 0.36). No differences in study-related adverse events, viral set point at 12 or 20 wk of open-ended interruption, viral resistance or therapy failure, retention of CD4 T cell numbers on ART, or retention of lymphoproliferative recall antigen responses were noted between groups. Importantly, resistance detected shortly after initial viremia following the open-ended TI did not result in a lack of resuppression to less than 50 copies/ml after reinitiation of the same drug regimen.Conclusion
Cycles of 2- to 6-wk time-fixed TIs in patients with suppressed HIV infection failed to confer a clinically significant benefit with regard to viral suppression off ART. Also, secondary analysis showed no difference between the two strategies in terms of safety, retention of immune reconstitution, and clinical therapy failure. Based on these findings, we suggest that further clinical research on the long-term consequences of TI strategies to decrease drug exposure is warranted. 相似文献100.
Alpha-catenin has often been considered to be a non-regulatory intercellular adhesion protein, in contrast to beta-catenin, which has well-documented dual roles in cell-cell adhesion and signal transduction. Recently, however, alpha-catenin has been found to be important not only in connecting the E-cadherin-beta-catenin complex to the actin cytoskeleton, but also in coordinating actin dynamics and inversely correlating cell adhesion with proliferation. As the number of alpha-catenin-interacting partners increases, intriguing new connections imply even more complex regulatory functions for this protein. 相似文献