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   17854篇
  免费   1415篇
  国内免费   1599篇
  20868篇
  2024年   42篇
  2023年   226篇
  2022年   606篇
  2021年   1005篇
  2020年   660篇
  2019年   801篇
  2018年   758篇
  2017年   522篇
  2016年   745篇
  2015年   1114篇
  2014年   1334篇
  2013年   1388篇
  2012年   1662篇
  2011年   1470篇
  2010年   900篇
  2009年   818篇
  2008年   902篇
  2007年   798篇
  2006年   722篇
  2005年   672篇
  2004年   518篇
  2003年   473篇
  2002年   369篇
  2001年   297篇
  2000年   277篇
  1999年   271篇
  1998年   170篇
  1997年   158篇
  1996年   181篇
  1995年   136篇
  1994年   154篇
  1993年   98篇
  1992年   113篇
  1991年   108篇
  1990年   79篇
  1989年   72篇
  1988年   48篇
  1987年   55篇
  1986年   38篇
  1985年   28篇
  1984年   37篇
  1983年   18篇
  1982年   14篇
  1981年   9篇
  1979年   2篇
排序方式: 共有10000条查询结果,搜索用时 0 毫秒
91.
This paper aimed to analyze antibody responses to SARS-CoV-2 in various populations. Two hundred and six COVID-19 patients, 46 convalescent patients, and 270 healthy population were enrolled. Antibodies against nucleocapsid protein (N) and spike protein's receptor-binding domain (RBD), and neutralizing antibody were detected. The results demonstrated both anti-N and anti-RBD antibodies could be detected in about 80% of COVID-19 patients and 90% of convalescent patients, while no antibodies could be detected in some convalescents and patients even after 14 days post-onset of symptoms. The level of anti-RBD antibody strongly correlated with the neutralizing activity of sera from these two cohorts. The titer of neutralizing antibody was lower in convalescents than that in active COVID-19 patients. In addition, the titer of neutralizing antibody was less than 1:80 in none of the severe COVID-19 patients, 18.8% in non-severe COVID-19 patients, and 32.6% in convalescents. The study suggests that the level of anti-RBD antibody is closely related to neutralization activity in COVID-19 patients and convalescents. Some SARS-CoV-2-infected cases trigger a weak antiviral immune response, and the level of neutralizing antibody may have a faster decay rate.  相似文献   
92.
Necroptosis is a unique programmed death mechanism of necrotic cells. However, its role and specific mechanism in cancer remain unclear, and a systematic pan‐cancer analysis of necroptosis is yet to be conducted. Thus, we performed a specific pan‐cancer analysis using The Cancer Genome Atlas and Genotype‐Tissue Expression databases to analyse necroptosis expression in terms of cancer prognosis, DNA methylation status, tumour mutative burden, microsatellite instability, immune cell infiltration in different types of cancer and molecular mechanisms. For the first time, we explored the correlation between necroptosis and immunotherapy prognosis. Thus, our study provides a relatively comprehensive understanding of the carcinogenicity of necroptosis in different types of cancer. It is suggested that necroptosis can be used to evaluate the sensitivity of different patients to immunotherapy and may become a potential target for tumour immunotherapy.  相似文献   
93.
Three processes play an important role in plant speciation: isolation, hybridization and polyploidization. Galapagos endemic Opuntia display putatively all of these processes. On this archipelago most islands are inhabited by a single Opuntia taxon. Santa Cruz, however, houses two morphologically distinct O. echios varieties (echios and gigantea). Morphological intermediates are found where these two geographically isolated varieties meet. Here we used ten microsatellite loci to reveal the population genetic structure of this system. In contrast to earlier studies, we found high genetic variability within localities. Genetic structuring was weak and no evidence for the existence of hybrids was found. The reasons for this weak genetic structure may include: the species’ hexaploid nature, high levels of gene flow, recent colonization, and the lack of geographic barriers. This first detailed genetic study on these threatened species will be important for further conservation planning.  相似文献   
94.
Studies on some plant species have shown that increasing the growth temperature gradually or pretreating with high temperature can lead to obvious photosynthetic acclimation to high temperature. To test whether this acclimation arises from heat adaptation of ribulose 1,5‐bisphosphate carboxylase/oxygenase (Rubisco, EC 4.1.1.39) activation mediated by Rubisco activase (RCA), gene expression of RCA large isoform (RCAL) and RCA small isoform (RCAS) in rice was determined using a 4‐day heat stress treatment [40/30°C (day/night)] followed by a 3‐day recovery under control conditions [30/22°C (day/night)]. The heat stress significantly induced the expression of RCAL as determined by both mRNA and protein levels. Correlative analysis indicated that RCAS protein content was extremely significantly related to Rubisco initial activity and net photosynthetic rate (Pn) under both heat stress and normal conditions. Immunoblot analysis of the Rubisco–RCA complex revealed that the ratio of RCAL to Rubisco increased markedly in heat‐acclimated rice leaves. Furthermore, transgenic rice plants expressing enhanced amounts of RCAL exhibited higher thermotolerance in Pn and Rubisco initial activity and grew better at high temperature than wild‐type (WT) plants and transgenic rice plants expressing enhanced amounts of RCAS. Under normal conditions, the transgenic rice plants expressing enhanced amounts of RCAS showed higher Pn and produced more biomass than transgenic rice plants expressing enhanced amounts of RCAL and wild‐type plants. Together, these suggest that the heat‐induced RCAL may play an important role in photosynthetic acclimation to moderate heat stress in vivo, while RCAS plays a major role in maintaining Rubisco initial activity under normal conditions.  相似文献   
95.
Ankyrin repeat, one of the most important protein motifs, plays a wide variety of roles in protein-protein interactions and in the signal pathways. Via large-scale sequencing, a novel 941-bp gene was isolated from an 18-week old human fetal brain cDNA library. It encodes a putative protein of 158 amino acid residues with four conserved ankyrin repeat domains. It displays a high degree of homology with rat low-density lipoprotein receptor-related protein 2-binding protein (Lrp2bp), and was therefore was named hLrp2bp (human Lrp2bp). The hLrp2bp gene was located in chromosome 4q35 and the conserved ankyrin repeat domains were located between amino acid residues 10 and 116. RT-PCR revealed that hLrp2bp was mainly expressed in the human testis, small intestine, colon and blood leukocytes, and in human pancreatic adenocarcinoma cells. A HEK293 cell was transfected with the ORF of hLrp2bp, and analyses showed that the protein was distributed both in the cytoplasm and nucleus.  相似文献   
96.
Obesity and its associated metabolic disorders such as diabetes, hepatic steatosis and chronic heart diseases are affecting billions of individuals. However there is no satisfactory drug to treat such diseases. In this study, we found that alisol A, a major active triterpene isolated from the Chinese traditional medicine Rhizoma Alismatis, could significantly attenuate high‐fat‐diet‐induced obesity. Our biochemical detection demonstrated that alisol A remarkably decreased lipid levels, alleviated glucose metabolism disorders and insulin resistance in high‐fat‐diet‐induced obese mice. We also found that alisol A reduced hepatic steatosis and improved liver function in the obese mice model.In addition, protein expression investigation revealed that alisol A had an active effect on AMPK/ACC/SREBP‐1c pathway. As suggested by the molecular docking study, such bioactivity of alisol A may result from its selective binding to the catalytic region of AMPK.Therefore, we believe that Alisol A could serve as a promising agent for treatment of obesity and its related metabolic diseases.  相似文献   
97.
Three new mycophenolic acid derivatives, penicacids A-C (1-3), together with two known analogues, mycophenolic acid (MPA, 4) and 4'-hydroxy-MPA (5), were isolated from a fungus Penicillium sp. SOF07 derived from a South China Sea marine sediment. The structures of compounds 1-3 were elucidated on the basis of MS and NMR ((1)H, (13)C, HSQC and HMBC) data analyses and comparisons with the known compounds. Structure-activity relationship studies of compounds 1-5 focused on inosine-monophosphate dehydrogenase inhibition revealed that hydroxylation at C-4', methylation at C-7-OH, dual hydroxylation at C-2'/C-3' double bond of MPA diminished bioactivity whereas glucosyl hydroxylation at C-4' correlated to bioactivity comparable to that observed for MPA.  相似文献   
98.
Lack of enhanced spinal regeneration in Nogo-deficient mice   总被引:37,自引:0,他引:37  
The failure of regeneration of severed axons in the adult mammalian central nervous system is thought to be due partly to the presence of endogenous inhibitors of axon regeneration. The nogo gene encodes three proteins (Nogo-A, -B, and -C) that have been proposed to contribute to this inhibition. To determine whether deletion of nogo enhances regenerative ability, we generated two lines of mutant mice, one lacking Nogo-A and -B but not -C (Nogo-A/B mutant), and one deficient in all three isoforms (Nogo-A/B/C mutant). Although Nogo-A/B-deficient myelin has reduced inhibitory activity in a neurite outgrowth assay in vitro, tracing of corticospinal tract fibers after dorsal hemisection of the spinal cord did not reveal an obvious increase in regeneration or sprouting of these fibers in either mouse line, suggesting that elimination of Nogo alone is not sufficient to induce extensive axon regeneration.  相似文献   
99.
100.
Activated rheumatoid arthritis (RA) fibroblast-like synoviocytes (RAFLSs) play a central role in both initiating and driving RA. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been documented to induce apoptosis only in a small proportion of RAFLSs, which is followed by an induction of proliferation in surviving cells. Apigenin, a chemopreventive bioflavonoid, exhibits proapoptotic activity in many types of cells. In the present study, we sought to determine whether apigenin could enhance the cytotoxic effect of TRAIL on activated RAFLSs. Human RAFLSs isolated from patients with RA were treated with TRAIL (1 nM), apigenin (20 μM), or their combination, and subjected to apoptosis analysis after a 24-h incubation and proliferation analysis after a 72-h incubation. Apoptosis assay revealed that TRAIL or apigenin alone induced a marked apoptosis in RAFLS and their combination yielded a synergistic increase in RAFLS apoptosis. Immunoblotting analysis of apoptosis regulators demonstrated that combined treatment with apigenin increased caspase-3 expression and activity and decreased the Bcl-2/Bax ratio relative to treatment with TRAIL alone. The presence of apigenin significantly restrained TRAIL-induced RAFLS proliferation, coupled with restoration of the expression of two cell-cycle inhibitors p21 and p27. Moreover, the combination with apigenin blunted TRAIL-induced activation of the phosphatidylinositol 3-kinase (PI3-K)/Akt pathway. Our data collectively demonstrate that apigenin sensitizes RAFLS to TRAIL-induced apoptosis and counteracts TRAIL-dependent RAFLS proliferation, which is likely mediated through inactivation of PI3-K/Akt signaling pathway.  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