全文获取类型
收费全文 | 6194篇 |
免费 | 662篇 |
国内免费 | 2篇 |
出版年
2022年 | 89篇 |
2021年 | 174篇 |
2020年 | 108篇 |
2019年 | 136篇 |
2018年 | 137篇 |
2017年 | 118篇 |
2016年 | 179篇 |
2015年 | 292篇 |
2014年 | 319篇 |
2013年 | 399篇 |
2012年 | 441篇 |
2011年 | 413篇 |
2010年 | 261篇 |
2009年 | 196篇 |
2008年 | 353篇 |
2007年 | 295篇 |
2006年 | 293篇 |
2005年 | 240篇 |
2004年 | 201篇 |
2003年 | 194篇 |
2002年 | 170篇 |
2001年 | 122篇 |
2000年 | 106篇 |
1999年 | 98篇 |
1998年 | 49篇 |
1997年 | 42篇 |
1996年 | 46篇 |
1995年 | 40篇 |
1994年 | 45篇 |
1993年 | 41篇 |
1992年 | 59篇 |
1991年 | 77篇 |
1990年 | 71篇 |
1989年 | 64篇 |
1988年 | 64篇 |
1987年 | 63篇 |
1986年 | 48篇 |
1985年 | 60篇 |
1984年 | 55篇 |
1983年 | 46篇 |
1982年 | 35篇 |
1981年 | 47篇 |
1980年 | 33篇 |
1979年 | 34篇 |
1978年 | 33篇 |
1977年 | 32篇 |
1975年 | 34篇 |
1973年 | 28篇 |
1972年 | 32篇 |
1971年 | 38篇 |
排序方式: 共有6858条查询结果,搜索用时 0 毫秒
221.
Stella Manta Vanessa Parmenopoulou Christos Kiritsis Athina Dimopoulou Nikolaos Kollatos Ioannis Papasotiriou 《Nucleosides, nucleotides & nucleic acids》2013,32(7):522-535
This article describes the synthesis of (3 ′S) and (3 ′R)-3 ′-amino-3 ′-deoxy pyranonucleosides and their precursors (3 ′S) and (3 ′R)-3 ′-azido-3 ′-deoxy pyranonucleosides. Azidation of 1,2:5,6-di-O-isopropylidene-3-O-toluenesulfonyl-α-D-allofuranose followed by hydrolysis and subsequent acetylation afforded 3-azido-3-deoxy-1,2,4,6-tetra-O-acetyl-D-glucopyranose, which upon coupling with the proper silylated bases, deacetylation, and catalytic hydrogenation, obtained the target 3 ′-amino-3 ′-deoxy-β-D-glucopyranonucleosides. The desired 1-(3 ′-amino-3 ′-deoxy-β-D-allopyranosyl)5-fluorouracil was readily prepared from the suitable imidazylate sugar after azidation followed by a protection/deprotection sequence and reduction of the unprotected azido precursor. No antiviral activity was observed for the novel nucleosides. Moderate cytostatic activity was recorded for the 5-fluorouracil derivatives. 相似文献
222.
Vanessa A.R.O. Vieira Tiago G. CorreiaRenata G. Moreira 《Comparative biochemistry and physiology. Toxicology & pharmacology : CBP》2013,157(1):1-8
We investigated the effects of acidic pH and acute aluminum (Al) exposure on the metabolic substrates of Astyanax bimaculatus, and on the ability of these animals to recover in clean water. After an acclimation period, sexually mature A. bimaculatus females were sorted into six glass aquaria with three experimental groups: control in neutral pH (7.0), acidic pH (5.5), and Al (0.5 mg·L− 1) in acidic pH (5.5). After a 96 h treatment, 10 animals from each experimental group were sampled and the rest were returned to clean water in neutral pH without Al for a recovery period of 96 h. The acidic pH, either alone or combined with Al, decreased T4 levels, whereas Al exposure increased T3 levels. Recovery of T3 levels occurred after 96 h. Al exposure decreased ovary and plasma proteins, muscle glycogen contents, and hepatic lipids due to lipoperoxidation. In the recovery phase, lipids decreased in most tissues, probably to re-establish ovary protein and hepatic glycogen. A. bimaculatus prioritized the use of energetic resources during acclimatization to Al instead of prioritizing reproduction, thereby avoiding the ovulation of impaired eggs. 相似文献
223.
Isabelle Vanessa Mohrenz Patrick Antonietti Stefan Pusch David Capper Jörg Balss Sophia Voigt Susanne Weissert Alicia Mukrowsky Jan Frank Christian Senft Volker Seifert Andreas von Deimling Donat Kögel 《Apoptosis : an international journal on programmed cell death》2013,18(11):1416-1425
Isocitrate dehydrogenase 1 (IDH1) decarboxylates isocitrate to α-ketoglutarate (α-KG) leading to generation of NADPH, which is required to regenerate reduced glutathione (GSH), the major cellular ROS scavenger. Mutation of R132 of IDH1 abrogates generation of α-KG and leads to conversion of α-KG to 2-hydroxyglutarate. We hypothesized that glioma cells expressing mutant IDH1 have a diminished antioxidative capacity and therefore may encounter an ensuing loss of cytoprotection under conditions of oxidative stress. Our study was performed with LN229 cells stably overexpressing IDH1 R132H and wild type IDH1 or with a lentiviral IDH1 knockdown. Quantification of GSH under basal conditions and following treatment with the glutathione reductase inhibitor BCNU revealed significantly lower GSH levels in IDH1 R132H expressing cells and IDH1 KD cells compared to their respective controls. FACS analysis of cell death and ROS production also demonstrated an increased sensitivity of IDH1-R132H-expressing cells and IDH1 KD cells to BCNU, but not to temozolomide. The sensitivity of IDH1-R132H-expressing cells and IDH1 KD cells to ROS induction and cell death was further enhanced with the transaminase inhibitor aminooxyacetic acid and under glutamine free conditions, indicating that these cells were more addicted to glutaminolysis. Increased sensitivity to BCNU-induced ROS production and cell death was confirmed in HEK293 cells inducibly expressing the IDH1 mutants R132H, R132C and R132L. Based on these findings we propose that in addition to its established pro-tumorigenic effects, mutant IDH1 may also limit the resistance of gliomas to specific death stimuli, therefore opening new perspectives for therapy. 相似文献
224.
Vanessa Dutra Silva Jeferson Schneider Carletto Eduardo Carasek Boris Ugarte Stambuk Maria da Graça Nascimento 《Process Biochemistry》2013,48(8):1159-1165
The α,β-unsaturated carbonyl compound (4S)-(+)-carvone was selectively reduced to (1R,2R,4S)-iso-dihydrocarveol using baker's yeasts. The conversion of the bioreduction reaction was monitored using a green hollow-fiber liquid–liquid–liquid microextraction (HF-LLLME) technique. Several parameters which may affect the bioreduction of (4S)-(+)-carvone, such as temperature, time, substrate/enzyme ratio, pH and buffer concentration, were evaluated. The effect of some additives, such as trehalose, DMSO and the ionic liquid [BMIm][PF6], was also studied. The (1R,2R,4S)-iso-dihydrocarveol was recovered with 52.7% conversion and diastereoisomeric excess >99% after 48 h of reaction at 40 °C in an aqueous monophasic system, with 0.1 mol L?1 buffer concentration (pH 7.5) and a substrate/yeast cell mass ratio of 8.0 mg g?1. The HF-LLLME microextraction technique allowed the optimization of the reaction with a reduction of over 99.5% in relation to the use of organic solvents. 相似文献
225.
226.
Marcelo de Oliveira Barbosa Rubens Rodrigues da Silva Vanessa Carolina de Sena Correia Luana Pereira dos Santos Analía del Valle Garnero Ricardo José Gunski 《Genetics and molecular biology》2013,36(1):70-73
Cytogenetic studies in birds are still scarce compared to other vertebrates. Woodcreepers (Dendrocolaptidae) are part of a highly specialized group within the Suboscines of the New World. They are forest birds exclusive to the Neotropical region and similar to woodpeckers, at a comparable evolutionary stage. This paper describes for the first time the karyotypes of the Olivaceous and the Narrow-billed Woodcreeper using conventional staining with Giemsa and silver nitrate staining of the nucleolar organizer regions (Ag-NORs). Metaphases were obtained by fibular bone marrow culture. The chromosome number of the Olivaceous Woodcreeper was 2n = 82 and of the Narrow-billed Woodcreeper, 2n = 82. Ag-NORs in the largest macrochromosome pair and evidence of a chromosome inversion are described herein for the first time for this group. 相似文献
227.
Jamie Bryant Vanessa M McDonald Allison Boyes Rob Sanson-Fisher Christine Paul Jessica Melville 《Respiratory research》2013,14(1):109
Adherence to medication among individuals with chronic obstructive pulmonary disease (COPD) is suboptimal and has negative impacts on survival and health care costs. No systematic review has examined the effectiveness of interventions designed to improve medication adherence. Electronic databases Medline and Cochrane were searched using a combination of MeSH and keywords. Eligible studies were interventions with a primary or secondary aim to improve medication adherence among individuals with COPD published in English. Included studies were assessed for methodological quality using the Effective Practice and Organisation of Care (EPOC) criteria. Of the 1,186 papers identified, seven studies met inclusion criteria. Methodological quality of the studies was variable. Five studies identified effective interventions. Strategies included: brief counselling; monitoring and feedback about inhaler use through electronic medication delivery devices; and multi-component interventions consisting of self-management and care co-ordination delivered by pharmacists and primary care teams. Further research is needed to establish the most effective and cost effective interventions. Special attention should be given to increasing patient sample size and using a common measure of adherence to overcome methodological limitations. Interventions that involve caregivers and target the healthcare provider as well as the patient should be further explored. 相似文献
228.
Genes encoding two proteins corresponding to elongation factor G (EF-G) were cloned from Pseudomonas aeruginosa. The proteins encoded by these genes are both members of the EFG I subfamily. The gene encoding one of the forms of EF-G is located in the str operon and the resulting protein is referred to as EF-G1A while the gene encoding the other form of EF-G is located in another part of the genome and the resulting protein is referred to as EF-G1B. These proteins were expressed and purified to 98% homogeneity. Sequence analysis indicated the two proteins are 90/84% similar/identical. In other organisms containing multiple forms of EF-G a lower degree of similarity is seen. When assayed in a poly(U)-directed poly-phenylalanine translation system, EF-G1B was 75-fold more active than EF-G1A. EF-G1A pre-incubate with ribosomes in the presence of the ribosome recycling factor (RRF) decreased polymerization of poly-phenylalanine upon addition of EF-G1B in poly(U)-directed translation suggesting a role for EF-G1A in uncoupling of the ribosome into its constituent subunits. Both forms of P. aeruginosa EF-G were active in ribosome dependent GTPase activity. The kinetic parameters (K
M) for the interaction of EF-G1A and EF-G1B with GTP were 85 and 70 μM, respectively. However, EF-G1B exhibited a 5-fold greater turnover number (observed k
cat) for the hydrolysis of GTP than EF-G1A; 0.2 s-1 vs. 0.04 s-1. These values resulted in specificity constants (k
cat
obs/K
M) for EF-G1A and EF-G1B of 0.5 x 103 s-1 M-1 and 3.0 x 103 s-1 M-1, respectively. The antibiotic fusidic acid (FA) completely inhibited poly(U)-dependent protein synthesis containing P. aeruginosa EF-G1B, but the same protein synthesis system containing EF-G1A was not affected. Likewise, the activity of EF-G1B in ribosome dependent GTPase assays was completely inhibited by FA, while the activity of EF-G1A was not affected. 相似文献
229.
Hung N. Luu E. Susan Amirian R. Palmer Beasley Linda Piller Wenyaw Chan Michael E. Scheurer 《PloS one》2013,8(11)
The Papanicolaou test (or Pap test) has long been used as a screening tool to detect cervical precancerous/cancerous lesions. However, studies on the use of this test to predict both the presence and change in size of genital warts are limited. We examined whether cervical Papanicolaou test results are associated with the size of the largest anal wart over time in HIV-infected women in an on-going cohort study in the US. A sample of 976 HIV-infected women included in a public dataset obtained from the Women’s Interagency HIV Study (WIHS) was selected for analysis. A linear mixed model was performed to determine the relationship between the size of anal warts and cervical Pap test results. About 32% of participants had abnormal cervical Pap test results at baseline. In the adjusted model, a woman with a result of Atypia Squamous Cell Undetermined Significance/Low-grade Squamous Intraepithelial Lesion (ASCUS/LSIL) had an anal wart, on average, 12.81 mm2 larger than a woman with normal cervical cytology. The growth rate of the largest anal wart after each visit in a woman with ASCUS/LSIL was 1.56 mm2 slower than that of a woman with normal cervical results. However, they were not significant (P = 0.54 and P = 0.82, respectively). This is the first study to examine the relationship between cervical Pap test results and anal wart development in HIV-infected women. Even though no association between the size of anal wart and cervical Pap test results was found, a screening program using anal cytology testing in HIV-infected women should be considered. Further studies in cost-effectiveness and efficacy of an anal cytology test screening program are warranted. 相似文献
230.
Matthew Maddocks Vanessa Halliday Alpna Chauhan Victoria Taylor Annmarie Nelson Cathy Sampson Anthony Byrne Gareth Griffiths Andrew Wilcock 《PloS one》2013,8(12)