全文获取类型
收费全文 | 2261篇 |
免费 | 161篇 |
国内免费 | 64篇 |
出版年
2023年 | 26篇 |
2022年 | 32篇 |
2021年 | 35篇 |
2020年 | 54篇 |
2019年 | 79篇 |
2018年 | 119篇 |
2017年 | 83篇 |
2016年 | 88篇 |
2015年 | 96篇 |
2014年 | 190篇 |
2013年 | 257篇 |
2012年 | 119篇 |
2011年 | 204篇 |
2010年 | 123篇 |
2009年 | 126篇 |
2008年 | 111篇 |
2007年 | 103篇 |
2006年 | 84篇 |
2005年 | 79篇 |
2004年 | 66篇 |
2003年 | 51篇 |
2002年 | 46篇 |
2001年 | 16篇 |
2000年 | 16篇 |
1999年 | 20篇 |
1998年 | 15篇 |
1997年 | 12篇 |
1996年 | 16篇 |
1995年 | 10篇 |
1994年 | 10篇 |
1993年 | 20篇 |
1992年 | 12篇 |
1991年 | 10篇 |
1990年 | 11篇 |
1989年 | 11篇 |
1988年 | 9篇 |
1987年 | 6篇 |
1986年 | 6篇 |
1985年 | 13篇 |
1984年 | 22篇 |
1983年 | 14篇 |
1982年 | 14篇 |
1981年 | 10篇 |
1980年 | 7篇 |
1979年 | 8篇 |
1978年 | 6篇 |
1977年 | 11篇 |
1975年 | 4篇 |
1974年 | 3篇 |
1972年 | 1篇 |
排序方式: 共有2486条查询结果,搜索用时 15 毫秒
991.
In recent years increasing evidence has emerged suggesting that oxidative stress is involved in the pathophysiology of a number of inherited metabolic disorders. However the clinical use of classical antioxidants in these diseases has been poorly evaluated and so far no benefit has been demonstrated. l-Carnitine is an endogenous substance that acts as a carrier for fatty acids across the inner mitochondrial membrane necessary for subsequent beta-oxidation and ATP production. Besides its important role in the metabolism of lipids, l-carnitine is also a potent antioxidant (free radical scavenger) and thus may protect tissues from oxidative damage. This review addresses recent findings obtained from patients with some inherited neurometabolic diseases showing that l-carnitine may be involved in the reduction of oxidative damage observed in these disorders. For some of these diseases, reduced concentrations of l-carnitine may occur due to the combination of this compound to the accumulating toxic metabolites, especially organic acids, or as a result of protein restricted diets. Thus, l-carnitine supplementation may be useful not only to prevent tissue deficiency of this element, but also to avoid oxidative damage secondary to increased production of reactive species in these diseases. Considering the ability of l-carnitine to easily cross the blood–brain barrier, l-carnitine supplementation may also be beneficial in preventing neurological damage derived from oxidative injury. However further studies are required to better explore this potential. 相似文献
992.
Genes that are indispensable for survival are termed essential genes. The analysis and identification of essential genes are very important for understanding the minimal requirements of cellular survival and for practical purposes. Proteins do not exert their function in isolation of one another but rather interact together in PPI networks. A global analysis of protein interaction networks provides an effective way to elucidate the relationships between proteins. With the recent large-scale identifications of essential genes and the production of large amounts of PPIs in humans, we are able to investigate the topological properties and biological properties of essential genes. However, until recently, no one has ever investigated human essential genes using topological and biological properties. In this study, for the first time, 28 topological properties and 22 biological properties were used to investigate the characteristics of essential and non-essential genes in humans. Most of the properties were statistically discriminative between essential and non-essential genes. The F-score was used to estimate the essentiality of each property. The GO-enrichment analysis was performed to investigate the functions of the essential and non-essential genes. Finally, based on the topological features and the biological characteristics, a machine-learning classifier was constructed to predict the essential genes. The results of the jackknife test and 10-fold cross validation test are encouraging, indicating that our classifier is an effective human essential gene discovery method. 相似文献
993.
In this study, we evaluated a novel microsomal glutathione S-transferase3 (MGST3) gene from the dinoflagellate Prorocentrum minimum, and examined its expression pattern in response to copper-and nickel-induced stresses. The full length of PmMGST3 was 732 bp, ranging from the dinoflagellate splice leader (DinoSL) sequence to the poly (A) tail, covering a 441-bp ORF, 97-bp 5′UTR, and 194-bp 3′UTR. The PmMGST3 was up-regulated by metals, including copper and nickel. The highest up-regulation levels of the PmMGST3 were found under 0.1 mg/L copper and 0.5 mg/L nickel treatment, respectively. In addition, the PmMGST3 was gradually up-regulated by 0.1 mg/L copper with increasing exposure time. Furthermore, ROS production and reduced GSH was measured in the copper treated cells. A significant increased ROS production and reduced GSH were found in the copper treated cells. These results suggest that PmMGST3 may be related to defense mechanisms associated with oxidative stress in dinoflagellates. 相似文献
994.
Zehra Agha Zafar Iqbal Maleeha Azam Maimoona Siddique Marjolein H. Willemsen Tjitske Kleefstra Christiane Zweier Nicole de Leeuw Raheel Qamar Hans van Bokhoven 《Gene》2014
We report on a consanguineous Pakistani family with a severe congenital microcephaly syndrome resembling the Seckel syndrome and Jawad syndrome. The affected individuals in this family were born to consanguineous parents of whom the mother presented with mild intellectual disability (ID), epilepsy and diabetes mellitus. The two living affected brothers presented with microcephaly, white matter disease of the brain, hyponychia, dysmorphic facial features with synophrys, epilepsy, diabetes mellitus and ID. Genotyping with a 250K SNP array in both affected brothers revealed an 18 MB homozygous region on chromosome 18p11.21-q12.1 encompassing the SCKL2 locus of the Seckel and Jawad syndromes. Sequencing of the RBBP8 gene, underlying the Seckel and Jawad syndromes, identified the novel mutation c.919A > G, p.Arg307Gly, segregating in a recessive manner in the family. In addition, in the two affected brothers and their mother we have also found a heterozygous 607 kb deletion, encompassing exons 13–19 of NRXN1. Bidirectional sequencing of the coding exons of NRXN1 did not reveal any other mutation on the other allele. It thus appears that the phenotype of the mildly affected mother can be explained by the NRXN1 deletion, whereas the more severe and complex microcephalic phenotype of the two affected brothers is due to the simultaneous deletion in NRXN1 and the homozygous missense mutation affecting RBBP8. 相似文献
995.
Giuseppina Raspaglio Marco Petrillo Enrica Martinelli Domenica Donatella Li Puma Marisa Mariani Marta De Donato Flavia Filippetti Simona Mozzetti Silvia Prislei Gian Franco Zannoni Giovanni Scambia Cristiano Ferlini 《Gene》2014
SOX9 [(sex determining region Y)-box9] gene has been implicated in the development and progression of different neoplasms. This study investigated the role of Sox9 in the expression of TUBB3 gene, a marker of aggressiveness in ovarian cancer (OC), encoding βIII-tubulin protein. Gene expression was assessed by quantitative polymerase chain reaction (qPCR) in OC models. 相似文献
996.
Jen-Lee Yang 《Biological research》2014,47(1)
Background
Acute toxicity testing were carried out the freshwater swamp shrimp, Macrobrachium nipponense, as the model animal for the semiconductor applied metals (gallium, antimony, indium, cadmium, and copper) to evaluate if the species is an suitable experimental animal of pollution in aquatic ecosystem.Results
The static renewal test method of acute lethal concentrations determination was used, and water temperature was maintained at 24.0 ± 0.5°C. Data of individual metal obtained from acute toxicity tests were determined using probit analysis method. The median lethal concentration (96-h LC50) of gallium, antimony, indium, cadmium, and copper for M. nipponense were estimated as 2.7742, 1.9626, 6.8938, 0.0539, and 0.0313 mg/L, respectively.Conclusions
Comparing the toxicity tolerance of M. nipponense with other species which exposed to these metals, it is obviously that the M. nipponense is more sensitive than that of various other aquatic animals. 相似文献997.
目的建立用Vero细胞检测柯萨奇病毒A组16型(CA16)滴度的方法,并对其适用性进行初步验证。方法通过对细胞种类的选择、细胞接种浓度和细胞病变判定时间的优化,建立测定CA16滴度的半数细胞感染剂量法(CCID50法),并对其进行初步验证。结果通过对病毒感染后细胞病变情况的观察,确定了以Vero细胞作为CA16病毒滴度检定用细胞。Vero细胞的最佳接种浓度和结果判定时间分别为5×104~1×105细胞/mL(即96孔板内每孔加入的最终细胞量为5×103~1×104细胞)和7 d。由4组人员对6批CA16病毒液进行重复检测,实验结果表明不同实验人员测定结果的变异系数(CV)在1.739%~4.974%之间,说明该方法测定结果重复性好,准确度高。结论该法简便、稳定,可以灵敏、准确地检测CA16病毒的滴度,可用于相关疫苗生产过程中的质量控制。 相似文献
998.
999.
Colleen A. McNaney Yulia Benitex David Luchetti Jeffrey M. Labasi Timothy V. Olah Daniel G. Morgan Dieter M. Drexler 《Analytical biochemistry》2014
l-Serine-O-phosphate (l-SOP), the precursor of l-serine, is a potent agonist against the group III metabotropic glutamate receptors (mGluRs) and, thus, is of interest as a potential biomarker for monitoring modulation of neurotransmitter release. So far, no reports are available on the analysis of l-SOP in cerebrospinal fluid (CSF). Here a novel method is presented to determine l-SOP levels in CSF employing precolumn derivatization with (5-N-succinimidoxy-5-oxopentyl)triphenylphosphonium bromide (SPTPP) coupled to liquid chromatography/mass spectrometry (derivatization–LC/MS, d-LC/MS). 相似文献
1000.
Juraj Simunić Dražen Petrov Tahar Bouceba Nédia Kamech Monica Benincasa Davor Juretić 《生物化学与生物物理学报:生物膜》2014
A method based on the use of signal peptide sequences from antimicrobial peptide (AMP) precursors was used to mine a placozoa expressed sequence tag database and identified a potential antimicrobial peptide from Trichoplax adhaerens. This peptide, with predicted sequence FFGRLKSVWSAVKHGWKAAKSR is the first AMP from a placozoan species, and was named trichoplaxin. It was chemically synthesized and its structural properties, biological activities and membrane selectivity were investigated. It adopts an α-helical structure in contact with membrane-like environments and is active against both Gram-negative and Gram-positive bacterial species (including MRSA), as well as yeasts from the Candida genus. The cytotoxic activity, as assessed by the haemolytic activity against rat erythrocytes, U937 cell permeabilization to propidium iodide and MCF7 cell mitochondrial activity, is significantly lower than the antimicrobial activity. In tests with membrane models, trichoplaxin shows high affinity for anionic prokaryote-like membranes with good fit in kinetic studies. Conversely, there is a low affinity for neutral eukaryote-like membranes and absence of a dose dependent response. With high selectivity for bacterial cells and no homologous sequence in the UniProt, trichoplaxin is a new potential lead compound for development of broad-spectrum antibacterial drugs. 相似文献