首页 | 本学科首页   官方微博 | 高级检索  
文章检索
  按 检索   检索词:      
出版年份:   被引次数:   他引次数: 提示:输入*表示无穷大
  收费全文   99154篇
  免费   776篇
  国内免费   887篇
  100817篇
  2022年   43篇
  2021年   68篇
  2020年   60篇
  2019年   52篇
  2018年   11909篇
  2017年   10733篇
  2016年   7553篇
  2015年   809篇
  2014年   543篇
  2013年   588篇
  2012年   4627篇
  2011年   13148篇
  2010年   12247篇
  2009年   8428篇
  2008年   10106篇
  2007年   11693篇
  2006年   594篇
  2005年   834篇
  2004年   1276篇
  2003年   1323篇
  2002年   1079篇
  2001年   346篇
  2000年   217篇
  1999年   108篇
  1998年   112篇
  1997年   85篇
  1996年   70篇
  1995年   76篇
  1994年   83篇
  1993年   104篇
  1992年   86篇
  1991年   89篇
  1990年   67篇
  1989年   49篇
  1988年   70篇
  1987年   57篇
  1986年   46篇
  1985年   49篇
  1984年   66篇
  1983年   60篇
  1982年   45篇
  1981年   41篇
  1980年   47篇
  1979年   41篇
  1978年   41篇
  1974年   39篇
  1972年   275篇
  1971年   301篇
  1969年   34篇
  1962年   34篇
排序方式: 共有10000条查询结果,搜索用时 0 毫秒
881.
Zinc plays a role in alleviating oxidative stress. However, the related mechanisms remain to be further elucidated. The present study was conducted to investigate whether the recovery of oxidative stress in high-fat-diet (HFD)-pretreated mice was affected by zinc. Male mice received either an HFD or a low-fat-diet (LFD) for 8 weeks. Then, the mice fed with HFD and LFD were both assigned to either a control diet (30 mg zinc, ZD) or a no-added zinc diet (NZD) for an additional 4 weeks. The results showed that after feeding with NZD for 4 weeks, the HFD-pretreated mice had the highest plasma glucose and insulin concentrations, while had the lowest CuZn-SOD and glutathione concentrations. Moreover, after feeding with NZD for 4 weeks, the HFD-pretreated mice had the highest hepatic ROS and homocysteine concentrations, while had the lowest glutathione and methionine concentrations. Furthermore, the HFD-pretreated mice fed with NZD for 4 weeks had the lowest gene and protein expression of betaine homocysteine-S-methyltransferase (BHMT), cystathionine β-synthase, and Sp1. The results suggested that zinc was critical for oxidative stress alleviation and homocysteine clearance in HFD-pretreated mice. It was further elucidated that improved Sp1 and BHMT expression are involved in the effects of zinc on oxidative stress.  相似文献   
882.
Since the mid-twentieth century, numerous vertebrates and invertebrates have been used as model organisms and become indispensable tools for exploring a broad range of biological and ecological processes. Crayfish seem to be adequate models which resulted in their involvement in research. In the two decades since its discovery, ongoing research has confirmed that the marbled crayfish (Procambarus virginalis Lyko, 2017) is an ideal taxon in this regard, especially due to its almost continuous asexual reproduction providing a source of genetically identical offspring. This review provides an overview of the occurrence, biology, ecology, ethology, and human exploitation of marbled crayfish with primary focus on its use as a laboratory model organism as well as potential risks to native biota in case of its introduction. Genetic uniformity, ease of culture, and a broad behaviour repertoire fosters the use of marbled crayfish in epigenetics and developmental biology, as well as physiological, ecotoxicological, and ethological research. Marbled crayfish could be further exploited for basic and applied fields of science such as evolutionary biology and clonal tumour evolution. However, due to its high invasive potential in freshwater environments security measures must be taken to prevent its escape into the wild.  相似文献   
883.
Multi-protein complexes, termed “inflammasomes,” are known to contribute to neuronal cell death and brain injury following ischemic stroke. Ischemic stroke increases the expression and activation of nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) Pyrin domain containing 1 and 3 (NLRP1 and NLRP3) inflammasome proteins and both interleukin (IL)-1β and IL-18 in neurons. In this study, we provide evidence that activation of either the NF-κB and MAPK signaling pathways was partly responsible for inducing the expression and activation of NLRP1 and NLRP3 inflammasome proteins and that these effects can be attenuated using pharmacological inhibitors of these two pathways in neurons and brain tissue under in vitro and in vivo ischemic conditions, respectively. Moreover, these findings provided supporting evidence that treatment with intravenous immunoglobulin (IVIg) preparation can reduce activation of the NF-κB and MAPK signaling pathways resulting in decreased expression and activation of NLRP1 and NLRP3 inflammasomes, as well as increasing expression of anti-apoptotic proteins, Bcl-2 and Bcl-xL, in primary cortical neurons and/or cerebral tissue under in vitro and in vivo ischemic conditions. In summary, these results provide compelling evidence that both the NF-κB and MAPK signaling pathways play a pivotal role in regulating the expression and activation of NLRP1 and NLRP3 inflammasomes in primary cortical neurons and brain tissue under ischemic conditions. In addition, treatment with IVIg preparation decreased the activation of the NF-κB and MAPK signaling pathways, and thus attenuated the expression and activation of NLRP1 and NLRP3 inflammasomes in primary cortical neurons under ischemic conditions. Hence, these findings suggest that therapeutic interventions that target inflammasome activation in neurons may provide new opportunities in the future treatment of ischemic stroke.  相似文献   
884.

Key message

Thirty significant associations between 22 SNPs and five plant architecture component traits in Chinese upland cotton were identified via GWAS. Four peak SNP loci located on chromosome D03 were simultaneously associated with more plant architecture component traits. A candidate gene, Gh_D03G0922, might be responsible for plant height in upland cotton.

Abstract

A compact plant architecture is increasingly required for mechanized harvesting processes in China. Therefore, cotton plant architecture is an important trait, and its components, such as plant height, fruit branch length and fruit branch angle, affect the suitability of a cultivar for mechanized harvesting. To determine the genetic basis of cotton plant architecture, a genome-wide association study (GWAS) was performed using a panel composed of 355 accessions and 93,250 single nucleotide polymorphisms (SNPs) identified using the specific-locus amplified fragment sequencing method. Thirty significant associations between 22 SNPs and five plant architecture component traits were identified via GWAS. Most importantly, four peak SNP loci located on chromosome D03 were simultaneously associated with more plant architecture component traits, and these SNPs were harbored in one linkage disequilibrium block. Furthermore, 21 candidate genes for plant architecture were predicted in a 0.95-Mb region including the four peak SNPs. One of these genes (Gh_D03G0922) was near the significant SNP D03_31584163 (8.40 kb), and its Arabidopsis homologs contain MADS-box domains that might be involved in plant growth and development. qRT-PCR showed that the expression of Gh_D03G0922 was upregulated in the apical buds and young leaves of the short and compact cotton varieties, and virus-induced gene silencing (VIGS) proved that the silenced plants exhibited increased PH. These results indicate that Gh_D03G0922 is likely the candidate gene for PH in cotton. The genetic variations and candidate genes identified in this study lay a foundation for cultivating moderately short and compact varieties in future Chinese cotton-breeding programs.
  相似文献   
885.
Acidophilic microorganisms involved in uranium bioleaching are usually suppressed by dissolved fluoride ions, eventually leading to reduced leaching efficiency. However, little is known about the regulation mechanisms of microbial resistance to fluoride. In this study, the resistance of Acidithiobacillus ferrooxidans ATCC 23270 to fluoride was investigated by detecting bacterial growth fluctuations and ferrous or sulfur oxidation. To explore the regulation mechanism, a whole genome microarray was used to profile the genome-wide expression. The fluoride tolerance of A. ferrooxidans cultured in the presence of FeSO4 was better than that cultured with the S0 substrate. The differentially expressed gene categories closely related to fluoride tolerance included those involved in energy metabolism, cellular processes, protein synthesis, transport, the cell envelope, and binding proteins. This study highlights that the cellular ferrous oxidation ability was enhanced at the lower fluoride concentrations. An overview of the cellular regulation mechanisms of extremophiles to fluoride resistance is discussed.  相似文献   
886.
Ribonucleotide reduction is the only known biological means for de novo production of deoxyribonucleotides, the building blocks of DNA. These are produced from ribonucleotides, the building blocks of RNA, and the direction of this reaction has been taken to support the idea that, in evolution, RNA preceded DNA as genetic material. However, an understanding of the evolutionary relationships among the three modern-day classes of ribonucleotide reductase and how the first reductase arose early in evolution is still far off. We propose that the diversification of this class of enzymes is inherently tied to microbial colonization of aerobic and anaerobic niches. The work is of broader interest, as it also sheds light on the process of adaptation to oxygenic environments consequent to the evolution of atmospheric oxygen.  相似文献   
887.
Fang DH  Fan CH  Ji Q  Qi BX  Li J  Wang L 《Molecular biology reports》2012,39(6):6801-6809
Paraoxonase is an HDL-associated enzyme that plays a preventive role against oxidative stress, which is thought to contribute to cancer development. PON1 activity varies widely among individuals, which is in part related to two common nonsynonymous polymorphisms in the PON1 gene (Q192R and L55M). The polymorphisms in PON1 have been implicated in cancer risk. However, results from the studies to date have been conflicting. To clarify the association, a meta-analysis was performed for 7,073 cases and 9,520 controls from 25 published case–control studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of the association. Significant associations between PON1-L55M but not Q192R polymorphism and total cancer were observed from all the comparisons. In stratified analyses, PON1-55M allele was a risk factor for breast cancer. Similarly, increased risk was observed for prostate cancer (OR = 1.18, 95% CI: 1.01–1.36, P heterogeneity = 0.260) and Caucasian population (OR = 1.18, 95% CI: 1.02–1.38, P heterogeneity = 0.1) of the LM genotype, compared with the LL genotype. For PON1-Q192R polymorphism, PON1-192R allele was a decreased risk factor for cancer in the Asian group (RR vs QQ: OR = 0.61, 95% CI: 0.38–0.98, P heterogeneity = 0.268; QR vs QQ: OR = 0.71, 95% CI: 0.52–0.96, P heterogeneity = 0.130; RR + QR vs QQ: OR = 0.71, 95% CI: 0.53–0.95, P heterogeneity = 0.135). Although some modest bias could not be eliminated, this meta-analysis suggests that the PON1-55M allele is a risk factor for the development of cancer, in particular for breast cancer. Future studies with larger sample sizes are warranted to further evaluate these associations.  相似文献   
888.
To facilitate marker-assisted transfer of desirable genes for improvement of yield traits, we used a set of backcross recombinant inbred lines (BRIL) derived from two elite parental lines, ‘Zhenshan97’ and ‘93-11’, to resolve a quantitative trait loci (QTL) cluster for heading date and yield-related traits in rice. Four main-effect QTL (qHD6.1, qHD6.2, qHD7, and qHD8) and four epistatic QTL affecting heading date in the BRIL were detected in two experimental trials. The major QTL (qHD8) was confirmed in three heterogeneous inbred families (HIF) that segregated for this target region, and narrowed down to a 20-kb segment in a large HIF-derived population. qHD8 was found to interact with qHD7 and had a pleiotropic effect responsible for heading date and yield components. To test usability of the identified QTL in rice improvement, we further developed near-isogenic lines (NIL) containing one or more target genes by marker-assisted transfer of ‘93-11’ alleles at qHD8, qHD7, and qHD6.1, and the GS3 gene for grain size into ‘Zhenshan97’. The pyramid line NIL(qHD8 + GS3) had higher yield potential, longer grains, and a more suitable heading date than ‘Zhenshan97’. Comparison of the NIL showed existence of epistasis between alleles at different loci and background effect on qHD8, which are very important for pyramiding of desirable alleles at the target QTL. These results will be particularly useful not only to understand the genetic basis of yield-related traits but also to improve the efficiency of marker-assisted selection for favorable loci in rice breeding programs.  相似文献   
889.
Phytase improves as a feed supplement the nutritional quality of phytate-rich diets (e.g., cereal grains, legumes, and oilseeds) by hydrolyzing indigestible phytate (myo-inositol 1,2,3,4,5,6-hexakis dihydrogen phosphate) and increasing abdominal absorption of inorganic phosphates, minerals, and trace elements. Directed phytase evolution was reported for improving industrial relevant properties such as thermostability (pelleting process) or activity. In this study, we report the cloning, characterization, and directed evolution of the Yersinia mollaretii phytase (Ymphytase). Ymphytase has a tetrameric structure with positive cooperativity (Hill coefficient was 2.3) and a specific activity of 1,073?U/mg which is ~10 times higher than widely used fungal phytases. High-throughput prescreening methods using filter papers or 384-well microtiter plates were developed. Precise subsequent screening for thermostable and active phytase variants was performed by combining absorbance and fluorescence-based detection system in 96-well microtiter plates. Directed evolution yielded after mutant library generation (SeSaM method) and two-step screening (in total ~8,400 clones) a phytase variant with ~20% improved thermostability (58°C for 20?min; residual activity wild type ~34%; variant ~53%) and increased melting temperature (1.5°C) with a slight loss of specific activity (993?U/mg).  相似文献   
890.
A nearly complete turtle shell from the Late Cretaceous (Maastrichtian) Hell Creek Formation of Slope County, North Dakota, represents the most complete remains to date of a Mesozoic kinosternoid turtle and a new species, Hoplochelys clark nov. sp. The new taxon is diagnosable from other representatives of Hoplochelys by the plesiomorphic placement of the humeral/femoral sulcus behind the hyo/hypoplastral suture and the autapomorphic development of an interrupted median (neural) keel. All six previously named Paleocene (Puercan and Torrejonian) representatives of Hoplochelys lack diagnostic characters and are synonymized as Hoplochelys crassa. A phylogenetic analysis reveals that Hoplochelys spp. and Agomphus pectoralis are most parsimoniously placed within Kinosternoidea along the phylogenetic stem of the extant Mesoamerican River Turtle Dermatemys mawii, extending that taxon’s stem lineage from the early Eocene to the late Maastrichtian. The two primary crown lineages of Kinosternoidea are thus known from the Mesozoic and split prior to the late Campanian. The presence of a thickened cruciform plastron, true costiform processes, only three inframarginals, and the reduction of the medial contact of the abdominals are synapomorphies of Chelydroidea, the clade formed by Chelydridae and Kinosternoidae.  相似文献   
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号