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961.
摘要 目的:建立鼠巨细胞病毒(MCMV)感染BALB/c裸鼠肝脏损伤的模型。方法:健康SPF级BALB/c裸鼠10只随机分为实验组和对照组,每组5只。实验组小鼠每只经腹腔注射接种250 μL MCMV 病毒悬液,对照组小鼠每只腹腔接种250 μL DMEM 培养液,于接种后第7天处死,无菌分离其肝脏,通过测定肝组织谷丙转氨酶(ALT)、实时荧光定量PCR检测MCMV DNA拷贝数、苏木精-伊红(HE)染色等方法,观察裸鼠肝脏组织的受损情况。结果:所有实验组的裸鼠均出现了不同程度的腹水;实验组裸鼠测定的肝组织ALT值较对照组明显上升(P<0.05);实时荧光定量PCR检测出实验组裸鼠肝脏MCMV DNA呈阳性;实验组肝脏病理切片HE染色可见大量炎症细胞浸润,肝细胞嗜酸性变,可见不规则包涵体,而对照组正常。结论:经腹腔注射250 μL MCMV病毒悬液7天后成功构建了裸鼠肝脏损伤的模型,为探究人巨细胞病毒(HCMV)的发病机制以及抗病毒新药和疫苗的研发提供了有利条件。 相似文献
962.
963.
Markwardt F 《Purinergic signalling》2007,3(4):249-253
After the primary structure of P2X receptors had been identified, their function had to be characterized on the molecular
level. Since these ligand-gated ion channels become activated very quickly after binding of ATP, methods with adequate time
resolution have to be applied to investigate the early events induced by the agonist. Single-channel recordings were performed
to describe conformational changes on P2X2, P2X4, and P2X7 receptors induced by ATP and also by allosteric receptor modifiers. The main results of these studies and the models of P2X
receptor kinetics derived from these observations are reviewed here. The investigation of purinoceptors by means of the patch
clamp technique following site-directed mutagenesis will probably reveal more details of P2X receptor function at the molecular
level. 相似文献
964.
Kentarou Hashikami Makoto Asahina Kandai Nozu Kazumoto Iijima Michio Nagata Michiyasu Takeyama 《Biochemistry and Biophysics Reports》2019
Alport syndrome (AS) is an inherited disorder characterized by glomerular basement membrane (GBM) abnormality and development of chronic kidney disease at an early age. The cause of AS is a genetic mutation in type IV collagen, and more than 80% of patients have X-linked AS (XLAS) with mutation in COL4A5. Although the causal gene has been identified, mechanisms of progression have not been elucidated, and no effective treatment has been developed. In this study, we generated a Col4a5 mutant mouse harboring a nonsense mutation (R471X) obtained from a patient with XLAS using clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated system. Col4a5 mRNA and protein expressions were not observed in the kidneys of hemizygous R471X male mice. R471X mice showed proteinuria and hematuria. Pathology revealed progression of glomerulosclerosis and interstitial fibrosis by age. Electron microscopy identified irregular thickening in GBM accompanied by irregular lamination. These observations were consistent with the clinical and pathological features of patients with AS and other established models. In addition, our mice models develop end-stage renal disease at the median age of 28 weeks, much later compared to previous models much more consistent with clinical course of human XLAS. Our models have advantages for future experiments in regard with treatment for human XLAS. 相似文献
965.
While often presented as a single entity, mitochondrial diseases comprise a wide range of clinical, biochemical and genetic heterogeneous disorders. Among them, defects in the process of oxidative phosphorylation are the most prevalent. Despite intense research efforts, patients are still without effective treatment. An important part of the development of new therapeutics relies on predictive models of the pathology in order to assess their therapeutic potential. Since mitochondrial diseases are a heterogeneous group of progressive multisystemic disorders that can affect any organ at any time, the development of various in vivo models for the different diseases-associated genes defects will accelerate the search for effective therapeutics. Here, we review existing Drosophila melanogaster models for mitochondrial diseases, with a focus on alterations in oxidative phosphorylation, and discuss the potential of this powerful model organism in the process of drug target discovery.This article is part of a Directed Issue entitled: Energy Metabolism Disorders and Therapies. 相似文献
966.
967.
Karolina Połeć Aneta Wójcik Michał Flasiński Paweł Wydro Marcin Broniatowski Katarzyna Hąc-Wydro 《生物化学与生物物理学报:生物膜》2019,1861(6):1093-1102
Antifungal and herbicidal activity of terpenes, being the components of the essential oils, is directly related to the incorporation of these compounds into cellular membranes. Thus, the differences in the lipid composition of various pathogenic membranes may be the factor determining the activity of these molecules. One of the class of lipids, which form the membrane environment are sterols. The aim of this work was to compare the effect of two terpenes: terpinen-4-ol and eucalyptol on the monolayers formed by ergosterol and β – sitosterol, which are the components of fungi and plant membranes, respectively. The modifications in the sterol monolayer properties were investigated in the surface pressure-area measurements and penetration studies as well as in a micrometer scale (Brewster angle microscopy experiments) and in nanoscale (GIXD technique). It was evidenced that although at higher surface pressure the terpene molecules are in part removed from the interface, they are able to substantially modify the condensation, morphology and molecular organization of the sterol film. It was also found that the incorporation of terpenes into sterol films is comparable for both sterols, however, β – sitosterol monolayers properties are affected more strongly than ergosterol films. Finally, the analysis of the results of the studies performed on model membrane systems and the results of antimicrobial studies reported in literature, enabled us to suggest that the activity of terpenes depends on the membrane composition and that the sterol concentration may be important from the point of view of antifungal effect of terpinen-4-ol and eucalyptol. 相似文献
968.
969.
Mutation rate and pattern of microsatellites in common carp (<Emphasis Type="Italic">Cyprinus carpio</Emphasis> L.) 总被引:1,自引:0,他引:1
Microsatellites are popular molecular markers in genetic and evolutionary studies. Their mutational dynamics have been extensively
studied in humans and fruit flies, but few data were available in fish. By genotyping 55 individuals of a F1 pedigree, we
investigated the mutation rates and patterns of 49 microsatellites in one of the most important fresh water fish species,
the common carp (Cyprinus carpio L.). The overall mutation rate of the 49 loci was 5.56×10−4/locus/generation (95% confidence interval 1.52×10−4 and 1.63×10−3). The change of allele size was between +2 to −5 repeat units, assuming that the mutation allele arose from the parental
allele most similar in size to the mutant. 相似文献
970.
Assessment of hepatic integrity after ischemic preservation by isolated perfusion in vitro: the role of albumin 总被引:1,自引:0,他引:1
Isolated perfusion of rat livers (IPRL) represents an attractive set-up to be used as a an evaluative tool in the easy and reproducible assessment of liver injury, allowing for screening of new approaches to organ preservation without the expenditure of actual transplantation experiments. Depending on the pathology under investigation, controversy exists concerning the inclusion of albumin in the IPRL. The present study evaluates the use of bovine serum albumin (BSA), simultaneously comparing its effect on healthy and ischemically challenged livers in the same model. Rat livers were excised, flushed via portal vein with Histidine-Tryptophan-Ketoglutarate (HTK) solution and preserved for up to 18 h in HTK at 4 degrees C. Perfusion was performed with Krebs-Henseleit buffer with or without addition of 3% BSA. Control preparations were perfused without prior ischemic storage. In the described model, stability of the preparations was documented for up to 120 min of isolated perfusion and addition of 3% BSA had no adverse effects on the viability of nonischemic livers. While liver perfusion without albumin was inappropriate to reveal alterations in parenchymal or vascular integrity after 18 h of cold preservation, albumin in the perfusate significantly and gradually unmasked differences between nonischemic liver preparations and livers stored ischemically for 8 or 18 h. It could be shown that BSA did have a significant modulatory effect on hepatic induction of apoptosis after ischemia in reducing cleavage of caspase 3. The implementation of albumin is advocated since experimental results are pivotally influenced by the presence or absence of this physiologically constitutive compound in the perfusate. 相似文献