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   20674篇
  免费   1046篇
  国内免费   30篇
  2023年   178篇
  2022年   403篇
  2021年   770篇
  2020年   457篇
  2019年   487篇
  2018年   716篇
  2017年   660篇
  2016年   854篇
  2015年   993篇
  2014年   1249篇
  2013年   1716篇
  2012年   1798篇
  2011年   1587篇
  2010年   930篇
  2009年   830篇
  2008年   952篇
  2007年   907篇
  2006年   762篇
  2005年   685篇
  2004年   556篇
  2003年   471篇
  2002年   434篇
  2001年   352篇
  2000年   313篇
  1999年   286篇
  1998年   112篇
  1997年   83篇
  1996年   98篇
  1995年   86篇
  1994年   69篇
  1993年   62篇
  1992年   173篇
  1991年   164篇
  1990年   128篇
  1989年   111篇
  1988年   147篇
  1987年   120篇
  1986年   97篇
  1985年   99篇
  1984年   102篇
  1983年   54篇
  1982年   55篇
  1981年   55篇
  1980年   53篇
  1979年   75篇
  1978年   47篇
  1977年   57篇
  1976年   40篇
  1975年   36篇
  1974年   33篇
排序方式: 共有10000条查询结果,搜索用时 421 毫秒
981.
In Vitro Cellular & Developmental Biology - Plant - A reliable and economically feasible in vitro plant regeneration protocol has been standardized for the Psoralea corylifolia Linn. using...  相似文献   
982.
Microtubule associated tumor suppressor 1 (MTUS1) has been recognized as a tumor suppressor gene in multiple cancers. However, the molecular mechanisms underlying the regulation of MTUS1 are yet to be investigated. This study aimed to clarify the significance of DNA methylation in silencing MTUS1 expression. We report that MTUS1 acts as tumor suppressor in non-small cell lung carcinoma (NSCLC). Analysis of in silico database and subsequent knockdown of DNMT1 suggested an inverse correlation between DNMT1 and MTUS1 function. Interestingly, increased methylation at MTUS1 promoter is associated with low expression of MTUS1. Treatment with DNA methyltransferases (DNMTs) inhibitor, 5-aza-2′-deoxycytidine (AZA) leads to both reduced promoter methylation accompanied with enrichment of H3K9Ac and enhanced MTUS1 expression. Remarkably, knockdown of MTUS1 showed increased proliferation and migration of NSCLC cells in contrast to diminished proliferation and migration, upon treatment with AZA. We concluded that low expression of MTUS1 correlates to DNA methylation and histone deacetylation in human NSCLC.  相似文献   
983.
Lactation is a highly demanding event in mammals, including buffaloes. It modulates the partitioning of nutrients, energy utilization, and food intake of the mother to meet her own and infant's energy needs. Failure to satisfy these energy needs leads to Negative Energy Balance (NEB). Currently, the only available indirect NEB indicator is Body Condition Score (BCS). However, direct dependency of the BCS on the peak depletion of body fat causes its inefficient use in a dairy farm. Thus, to establish objective NEB indicators in buffaloes, the serum levels of biochemical (serum β-hydroxybutyrate [BHBA] and free fatty acids [FFAs]), and endocrine (Growth Hormone [GH], insulin-like growth factor1 [IGF1], Insulin, and leptin) parameters were estimated in buffaloes. Our results revealed that serum FFA levels were significantly (p < 0.05) higher in high milk yielders (HMY) than low milk yielders (LMY) and heifers (H) during the 3rd and the 4th weeks of postpartum. The serum FFA levels were also significantly (p < 0.001) higher in the postpartum buffaloes with BCS < 3 in the field conditions. Further, serum leptin levels were significantly (p < 0.05) lower in HMY than LMY during the 3rd week of postpartum. However, the BHBA, GH, IGF1, and insulin levels were not significantly different between lactating buffaloes and H. These observations indicated that the NEB condition is probably restricted to the first month of early lactation in buffaloes. In conclusion, the simultaneous higher FFA and lower leptin levels could act as direct plausible metabolic indicators of NEB in buffaloes.  相似文献   
984.
Senescence and autophagy play important roles in homeostasis. Cellular senescence and autophagy commonly cause several degenerative processes, including oxidative stress, DNA damage, telomere shortening, and oncogenic stress; hence, both events are known to be interrelated. Autophagy is well known for its disruptive effect on human diseases, and it is currently proposed to have a direct effect on triggering senescence and quiescence. However, it is yet to be proven whether autophagy has a positive or negative impact on senescence. It is known that elevated levels of autophagy induce cell death, whereas inadequate autophagy can trigger cellular senescence. Both have important roles in human diseases such as aging, renal degeneration, neurodegenerative disorders, and cancer. Therefore, this review aims to highlight the relevance of senescence and autophagy in selected human ailments through a summary of recent findings on the connection and effects of autophagy and senescence in these diseases.  相似文献   
985.
Resident cardiac progenitor cells (CPCs) have gained attention in cardiac regenerative medicine primarily due to their paracrine activity. In our current study we determined the role of pathological conditions such as heart failure on the autocrine-paracrine action of stem cell antigen-1 (Sca-1) expressing CPC. This comparative secretome profiling of Sca-1+ cells derived from transgenic heart failure (αMHC–cyclin-T1/Gαq overexpression [Cyc] cells) versus healthy (wild-type [Wt] cells) mice, achieved via mass-spectrometric quantification, enabled the identification of over 700 proteins. Our results demonstrate that the heart failure milieu caused a 2-fold enrichment of extracellular matrix proteins (ECM) like biglycan, versican, collagen XII, and angiogenic factors like heparan sulfate proteoglycan 2, plasminogen activator inhibitor 1 in the secretome. We further elucidated the direct influence of the secretome on the functional behavior of Sca-1 + cells via in vitro tube forming assay. Secreted factors present in the diseased milieu induced tube formation in Cyc cells (1.7-fold; p < 0.01) when compared with Wt cells after 24 hr of exposure. The presence of conditioned media moderately increased the proliferation of Cyc cells but had a more pronounced effect on Wt cells. Overall, these findings revealed global modifications in the secretory activity of adult Sca-1 + cells in the heart failure milieu. The secretion of ECM proteins and angiogenic factors, which are crucial for cardiac remodeling and recovery, was notably enriched in the supernatant of Cyc cells. Thus, during heart failure the microenvironment of Sca-1 + cells might favor angiogenesis and proliferation suggesting their potential to recover the damaged heart.  相似文献   
986.
An elevated level of homocysteine (Hcy) leads to hyperhomocysteinemia (HHcy), which results in vascular dysfunction and pathological conditions identical to stroke symptoms. Hcy increases oxidative stress and leads to increase in blood–brain barrier permeability and leakage. Hydrogen sulfide (H2S) production during the metabolism of Hcy has a cerebroprotective effect, although its effectiveness in Hcy-induced neurodegeneration and neurovascular permeability is less explored. Therefore, the current study was designed to perceive the neuroprotective effect of exogenous H 2S against HHcy, a cause of neurodegeneration. To test this hypothesis, we used four groups of mice: control, Hcy, control + sodium hydrosulfide hydrate (NaHS), and Hcy + NaHS, and an HHcy mice model in Swiss albino mice by giving a dose of 1.8 g of dl -Hcy/L in drinking for 8–10 weeks. Mice that have 30 µmol/L Hcy were taken for the study, and a H 2S supplementation of 20 μmol/L was given for 8 weeks to all groups of mice. HHcy results in the rise of the levels of superoxide and nitrite, although a concomitant decrease in the level of superoxide dismutase, catalase, glutathione peroxidase, reduced glutathione, and arginase in oxidative stress and a concomitant decrease in the endogenous level of H 2S. Although H 2S supplementation ameliorated, the effect of HHcy and the levels of H 2S returned to the average level in HHcy animals supplemented with H 2S. Interestingly, H 2S supplementation ameliorated neurovascular remodeling and neurodegeneration. Thus, our study suggested that H 2S could be a beneficial therapeutic candidate for the treatment of Hcy-associated neurodegeneration, such as stroke and neurovascular disorders.  相似文献   
987.
Diabetes affects a large population of the world. Lifestyle, obesity, dietary habits, and genetic factors contribute to this metabolic disease. A target pathway to control diabetes is the 5′-adenosine monophosphate-activated protein kinase (AMPK) signaling pathway. AMPK is a heterotrimeric protein with α, β, and γ subunits. In several studies, AMPK activation enhanced glucose uptake into cells and inhibited intracellular glucose production. Impairment of AMPK activity is present in diabetes, according to some studies. Drugs used in the treatment of diabetes, such as metformin, are also known to act through regulation of AMPK. Thus, drugs that activate and regulate AMPK are potential candidates for the treatment of diabetes. In addition, many patients encounter important adverse effects, like hypoglycemia, while using allopathic drugs. As a result, the investigation of plant-derived natural drugs that lack adverse side effects and treat diabetes is necessary. Natural products like berberine, quercetin, resveratrol, and so forth have shown significant potential in regulating and activating the AMPK pathway which can lead to manage diabetes mellitus and its complications.  相似文献   
988.
Skeletal muscle atrophy/wasting is associated with impaired protein metabolism in diverse physiological and pathophysiological conditions. Elevated levels of reactive oxygen species (ROS), disturbed redox status, and weakened antioxidant defense system are the major contributing factors toward atrophy. Regulation of protein metabolism by controlling ROS levels and its associated catabolic pathways may help in treating atrophy and related clinical conditions. Although cinnamaldehyde (CNA) enjoys the established status of antioxidant and its role in ROS management is reported, impact of CNA on skeletal muscle atrophy and related pathways is still unexplored. In the current study, the impact of CNA on C2C12 myotubes and the possible protection of cultured cells from H 2O 2-induced atrophy is examined. Myotubes were treated with H 2O 2 in the presence and absence of CNA and the changes in the antioxidative, proteolytic systems, and mitochondrial functions were scored. Morphological analysis showed significant protective effects of CNA on length, diameter, and nuclei fusion index of myotubes. The evaluation of biochemical markers of atrophy; creatine kinase, lactate dehydrogenase, succinate dehydrogenase along with the study of muscle-specific structural protein (i.e., myosin heavy chain-fast [MHCf] type) showed significant protection of proteins by CNA. CNA pretreatment not only checked the activation of proteolytic systems (ubiquitin-proteasome E3-ligases [MuRF1/Atrogin1]), autophagy [Beclin1/LC3B], cathepsin L, calpain, caspase), but also prevented any alteration in the activities of antioxidative defense enzymes (catalase, glutathione- S-transferase, glutathione-peroxidase, superoxide dismutase, glutathione reductase). The results suggest that CNA protects myotubes from H 2O 2-induced atrophy by inhibiting/resisting the amendments in proteolytic systems and maintains cellular redox-balance.  相似文献   
989.
The prognostic signatures play an essential role in the era of personalised therapy for cancer patients including lung adenocarcinoma (LUAD). Long noncoding RNA (LncRNA), a relatively novel class of RNA, has shown to play a crucial role in all the areas of cancer biology. Here, we developed and validated a robust LncRNA-based prognostic signature for LUAD patients using three different cohorts. In the discovery cohort, four LncRNAs were identified with 10% false discovery rate and a hazard ratio of >10 using univariate Cox regression analysis. A risk score, generated from the four LncRNAs’ expression, was found to be a significant predictor of survival in the discovery and validation cohort (p = 9.97 × 10 −8 and 1.41 × 10 −3, respectively). Further optimisation of four LncRNAs signature in the validation cohort, generated a three LncRNAs prognostic score (LPS), which was found to be an independent predictor of survival in both the cohorts ( p = 1.00 × 10 −6 and 7.27 × 10 −4, respectively). The LPS also significantly divided survival in clinically important subsets, including Stage I ( p = 9.00 × 10 −4 and 4.40 × 10 −2, respectively), KRAS wild-type (WT), KRAS mutant ( p = 4.00 × 10 −3 and 4.30 × 10 −2, respectively) and EGFR WT ( p = 2.00 × 10 −4). In multivariate analysis LPS outperformed, eight previous prognosticators. Further, individual members of LPS showed a significant correlation with survival in microarray data sets. Mutation analysis showed that high-LPS patients have a higher mutation rate and inactivation of the TP53 pathway. In summary, we identified and validated a novel LncRNA signature LPS for LUAD.  相似文献   
990.
The analysis of estrogen receptor (ER) expression in breast carcinomas plays a crucial role in determining the endocrine responsiveness of tumors for systemic adjuvant therapy. Conventionally, the ER levels in breast carcinomas had been detected using the dextran-coated charcoal assay and radioimmunoassay, which are now substituted with safer and economic antibody-based assays such as immunohistochemistry (IHC) and enzyme-linked immunosorbent assay (ELISA). Despite a gold (Au) standard method, the IHC has been criticized for factors such as tissue fixation, antibody selection, and threshold staining for result interpretation that could falsify test accuracy and reproducibility. The quest for alternative methods of ER quantification in tissue samples paved the way for aptamer-based diagnostics. Previously, we have isolated a DNA aptamer against human ER alpha (ERα) using an in vitro evolution system. In this study, we developed an electrochemical sensor using the 76-nucleotide DNA ERα- aptamer for rapid, precise, and cost-effective detection of ERα expression in human breast cancer patients. The aptasensor was constructed by covalently immobilizing the thiolated ERα- aptamer onto a screen-printed Au electrode. Construction of aptasensors was confirmed through atomic force microscopy and differential pulse voltammetry measurements. A detection limit of 0.001 ng/ml was calculated for full-length ERα (66.2 kDa) in a detection time of 10 min. Analysis of the cancerous breast tissue samples using the ELISA and aptasensor methods enabled distinctive classification of samples into the categories of ER −ve, weak ER +ve, and strong ER +ve samples. The current change of this aptasensor lies within 5% after a storage of 60 days at 4°C. Further studies on a reasonably large sample size are required to realize the clinical potential of the sensor.  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