全文获取类型
收费全文 | 4127篇 |
免费 | 330篇 |
国内免费 | 2篇 |
专业分类
4459篇 |
出版年
2023年 | 24篇 |
2022年 | 59篇 |
2021年 | 108篇 |
2020年 | 56篇 |
2019年 | 74篇 |
2018年 | 116篇 |
2017年 | 84篇 |
2016年 | 151篇 |
2015年 | 198篇 |
2014年 | 246篇 |
2013年 | 320篇 |
2012年 | 390篇 |
2011年 | 334篇 |
2010年 | 223篇 |
2009年 | 180篇 |
2008年 | 242篇 |
2007年 | 212篇 |
2006年 | 194篇 |
2005年 | 184篇 |
2004年 | 171篇 |
2003年 | 148篇 |
2002年 | 138篇 |
2001年 | 25篇 |
2000年 | 27篇 |
1999年 | 34篇 |
1998年 | 45篇 |
1997年 | 17篇 |
1996年 | 22篇 |
1995年 | 18篇 |
1994年 | 21篇 |
1993年 | 17篇 |
1992年 | 19篇 |
1991年 | 14篇 |
1990年 | 22篇 |
1989年 | 18篇 |
1988年 | 15篇 |
1987年 | 15篇 |
1985年 | 11篇 |
1984年 | 25篇 |
1983年 | 14篇 |
1982年 | 17篇 |
1981年 | 16篇 |
1980年 | 18篇 |
1979年 | 17篇 |
1978年 | 16篇 |
1977年 | 8篇 |
1974年 | 7篇 |
1973年 | 7篇 |
1964年 | 7篇 |
1962年 | 7篇 |
排序方式: 共有4459条查询结果,搜索用时 0 毫秒
71.
Irene Tsina Martin Kaloostian Rosy Lee Thomas Tarnowski Belinda Wong 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》1996,681(2):347
A method for the quantification of mycophenolate mofetil (MMF, CellCept) in plasma using solid-phase extraction and HPLC is described here. A solution of internal standard is added to a 0.5-ml plasma aliquot. The resulting sample is treated with water and dilute HCl and applied to a C18 solid-phase extraction column. After a water wash, the MMF and internal standard are eluted with methanol-0.1 M citrate-phosphate buffer, pH 2.6 (80:20, v/v). A 20-μl aliquot of the eluate is injected onto a C18 column (5 μm particle size, 150 × 4.6 mm I.D.) and eluted at ambient temperature with acetonitrile-0.05 M citrate-phosphate buffer, pH 3.6, containing 0.02 M heptanesulfonic acid (41:59, v/v). Quantification is achieved by UV detection at 254 nm. The method is reproducible, accurate and specific for MMF. Using 0.5 ml of plasma for analysis, the quantification limit is 0.400 μg/ml and the range is 0.400–20 μg/ml. Based on the stability profile of MMF in plasma, it is recommended that blood samples collected following intravenous infusion be immediately stored on ice and that plasma be prepared rapidly, immediately stored frozen at −80°C and analyzed within four months of collection. 相似文献
72.
73.
Background
A recent report from the British Nuffield Council on Bioethics associated ‘emerging biotechnologies’ with a threefold challenge: 1) uncertainty about outcomes, 2) diverse public views on the values and implications attached to biotechnologies and 3) the possibility of creating radical changes regarding societal relations and practices. To address these challenges, leading international institutions stress the need for public involvement activities (PIAs). The objective of this study was to assess the state of PIA reports in the field of biomedical research.Methods
PIA reports were identified via a systematic literature search. Thematic text analysis was employed for data extraction.Results
After filtering, 35 public consultation and 11 public participation studies were included in this review. Analysis and synthesis of all 46 PIA studies resulted in 6 distinguishable PIA objectives and 37 corresponding PIA methods. Reports of outcome translation and PIA evaluation were found in 9 and 10 studies respectively (20% and 22%). The paper presents qualitative details.Discussion
The state of PIAs on biomedical research and innovation is characterized by a broad range of methods and awkward variation in the wording of objectives. Better comparability of PIAs might improve the translation of PIA findings into further policy development. PIA-specific reporting guidelines would help in this regard. The modest level of translation efforts is another pointer to the “deliberation to policy gap”. The results of this review could inform the design of new PIAs and future efforts to improve PIA comparability and outcome translation. 相似文献74.
Irene Konstantopoulou Christos A. Ouzounis Elena Drosopoulou Minas Yiangou Paschalis Sideras Chris Sander Zacharias G. Scouras 《Journal of molecular evolution》1995,41(4):414-420
A clone isolated from a Drosophila auraria heat-shock cDNA library presents two long, antiparallel, coupled (LAC) open reading frames (ORFs). One strand ORF is 1,929 nucleotides long and exhibits great identity (87.5% at the nucleotide level and 94% at the amino acid level) with the hsp70 gene copies of D. melanogaster, while the second strand ORF, in antiparallel in-frame register arrangement, is 1,839 nucleotides long and exhibits 32% identity with a putative, recently identified, NAD+-dependent glutamate dehydrogenase (NAD+-GDH). The overlap of the two ORFs is 1,824 nucleotides long. Computational analysis shows that this LAC ORF arrangement is conserved in other hsp70 loci in a wide range of organisms, raising questions about possible evolutionary benefits of such a peculiar genomic organization.Correspondence to: Z.G. Scouras 相似文献
75.
RS Mehta A Rodriguez M Chico I Guadalupe N Broncano C Sandoval F Tupiza E Mitre PJ Cooper 《PLoS neglected tropical diseases》2012,6(7):e1753
Background
Children of mothers infected with soil-transmitted helminths (STH) may have an increased susceptibility to STH infection.Methods and Findings
We did a case-control study nested in a birth cohort in Ecuador. Data from 1,004 children aged 7 months to 3 years were analyzed. Cases were defined as children with Ascaris lumbricoides and/or Trichuris trichiura, controls without. Exposure was defined as maternal infection with A. lumbricoides and/or T. trichiura, detected during the third trimester of pregnancy. The analysis was restricted to households with a documented infection to control for infection risk. Children of mothers with STH infections had a greater risk of infection compared to children of uninfected mothers (adjusted OR 2.61, 95% CI: 1.88–3.63, p<0.001). This effect was particularly strong in children of mothers with both STH infections (adjusted OR: 5.91, 95% CI: 3.55–9.81, p<0.001). Newborns of infected mothers had greater levels of plasma IL-10 than those of uninfected mothers (p = 0.033), and there was evidence that cord blood IL-10 was increased among newborns who became infected later in childhood (p = 0.060).Conclusion
Our data suggest that maternal STH infections increase susceptibility to infection during early childhood, an effect that was associated with elevated IL-10 in cord plasma. 相似文献76.
Irene Martinez Haijun Gao George N. Bennett Ka-Yiu San 《Journal of industrial microbiology & biotechnology》2018,45(1):53-60
Several metabolic engineered Escherichia coli strains were constructed and evaluated for four-carbon dicarboxylic acid production. Fumarase A, fumarase B and fumarase C single, double and triple mutants were constructed in a ldhA adhE mutant background overexpressing the pyruvate carboxylase from Lactococcus lactis. All the mutants produced succinate as the main four-carbon (C4) dicarboxylic acid product when glucose was used as carbon source with the exception of the fumAC and the triple fumB fumAC deletion strains, where malate was the main C4-product with a yield of 0.61–0.67 mol (mole glucose)?1. Additionally, a mdh mutant strain and a previously engineered high-succinate-producing strain (SBS550MG-Cms pHL413-Km) were investigated for aerobic malate production from succinate. These strains produced 40.38 mM (5.41 g/L) and 50.34 mM (6.75 g/L) malate with a molar yield of 0.53 and 0.55 mol (mole succinate)?1, respectively. Finally, by exploiting the high-succinate production capability, the strain SBS550MG-Cms243 pHL413-Km showed significant malate production in a two-stage process from glucose. This strain produced 133 mM (17.83 g/L) malate in 47 h, with a high yield of 1.3 mol (mole glucose)?1 and productivity of 0.38 g L?1 h?1. 相似文献
77.
78.
The amount and architecture of vigilance states are governed by two distinct processes, which occur at different time scales. The first, a slow one, is related to a wake/sleep dependent homeostatic Process S, which occurs on a time scale of hours, and is reflected in the dynamics of NREM sleep EEG slow-wave activity. The second, a fast one, is manifested in a regular alternation of two sleep states – NREM and REM sleep, which occur, in rodents, on a time scale of ∼5–10 minutes. Neither the mechanisms underlying the time constants of these two processes – the slow one and the fast one, nor their functional significance are understood. Notably, both processes are primarily apparent during sleep, while their potential manifestation during wakefulness is obscured by ongoing behaviour. Here, we find, in mice provided with running wheels, that the two sleep processes become clearly apparent also during waking at the level of behavior and brain activity. Specifically, the slow process was manifested in the total duration of waking periods starting from dark onset, while the fast process was apparent in a regular occurrence of running bouts during the waking periods. The dynamics of both processes were stable within individual animals, but showed large interindividual variability. Importantly, the two processes were not independent: the periodic structure of waking behaviour (fast process) appeared to be a strong predictor of the capacity to sustain continuous wakefulness (slow process). The data indicate that the temporal organization of vigilance states on both the fast and the slow time scales may arise from a common neurophysiologic mechanism. 相似文献
79.
We have used the HLA-C-specific DNA probe pC250 to investigate restriction fragment length polymorphism (RFLP) at the HLA-C locus. Genomic Southern blot hybridization included DNA prepared from a panel of homozygous typing cells representing serological specificities Cw1 to Cw8 and also from samples representing Cw blanks. Although many restriction nucleases failed to reveal any polymorphism, RFLPs were evident with Taq I, Pvu II, Bst XI, Nde 1, and Nci I in addition to the previously reported Eco RI. In the case of Bst XI, a unique RFLP defined a subset of serologically defined Cw blanks. Comparison of RFLP sizes with restriction fragment lengths obtained from the known HLA-Cw3 gene sequence permitted the localization of intragenic C locus RFLLs and the identification of a variable Taq I site in the second intron, a variable Nci I site near the end of the fourth exon, and a variable Pvu lI site in the fifth intron. 相似文献
80.
Ana Casa?al Ulrich Zander Cristina Mu?oz Florine Dupeux Irene Luque Miguel Angel Botella Wilfried Schwab Victoriano Valpuesta José A. Marquez 《The Journal of biological chemistry》2013,288(49):35322-35332
Pathogenesis-related 10 (PR-10) proteins are involved in many aspects of plant biology but their molecular function is still unclear. They are related by sequence and structural homology to mammalian lipid transport and plant abscisic acid receptor proteins and are predicted to have cavities for ligand binding. Recently, three new members of the PR-10 family, the Fra a proteins, have been identified in strawberry, where they are required for the activity of the flavonoid biosynthesis pathway, which is essential for the development of color and flavor in fruits. Here, we show that Fra a proteins bind natural flavonoids with different selectivity and affinities in the low μm range. The structural analysis of Fra a 1 E and a Fra a 3-catechin complex indicates that loops L3, L5, and L7 surrounding the ligand-binding cavity show significant flexibility in the apo forms but close over the ligand in the Fra a 3-catechin complex. Our findings provide mechanistic insight on the function of Fra a proteins and suggest that PR-10 proteins, which are widespread in plants, may play a role in the control of secondary metabolic pathways by binding to metabolic intermediates. 相似文献