全文获取类型
收费全文 | 22174篇 |
免费 | 1522篇 |
国内免费 | 986篇 |
专业分类
24682篇 |
出版年
2024年 | 53篇 |
2023年 | 295篇 |
2022年 | 631篇 |
2021年 | 1014篇 |
2020年 | 674篇 |
2019年 | 900篇 |
2018年 | 889篇 |
2017年 | 679篇 |
2016年 | 958篇 |
2015年 | 1335篇 |
2014年 | 1511篇 |
2013年 | 1752篇 |
2012年 | 1949篇 |
2011年 | 1819篇 |
2010年 | 1016篇 |
2009年 | 907篇 |
2008年 | 1012篇 |
2007年 | 928篇 |
2006年 | 845篇 |
2005年 | 724篇 |
2004年 | 632篇 |
2003年 | 526篇 |
2002年 | 475篇 |
2001年 | 309篇 |
2000年 | 320篇 |
1999年 | 282篇 |
1998年 | 174篇 |
1997年 | 161篇 |
1996年 | 181篇 |
1995年 | 162篇 |
1994年 | 136篇 |
1993年 | 102篇 |
1992年 | 151篇 |
1991年 | 150篇 |
1990年 | 124篇 |
1989年 | 97篇 |
1988年 | 98篇 |
1987年 | 101篇 |
1986年 | 70篇 |
1985年 | 89篇 |
1984年 | 50篇 |
1983年 | 53篇 |
1982年 | 27篇 |
1981年 | 26篇 |
1980年 | 24篇 |
1979年 | 35篇 |
1978年 | 28篇 |
1977年 | 20篇 |
1975年 | 29篇 |
1974年 | 21篇 |
排序方式: 共有10000条查询结果,搜索用时 0 毫秒
991.
Some studies have shown that IL-18 was associated with aetiology and progression of asthma. However, the association between
single-nucleotide polymorphisms −607C/A (rs1946518) and −137G/C (rs187238) located in the IL-18 gene promoter and asthma risk
was still controversial and ambiguous. To derive a more precise effect on the association between these polymorphisms and
asthma risk, we performed a meta-analysis based on the currently available evidence of the literature. A total of 5 studies
with 1411 cases and 1525 controls for −607C/A polymorphism and 5 studies with 1883 cases and 6645 controls for −137G/C polymorphism
were identified to perform a meta-analysis, up to October 2010. Summary ORs and corresponding 95% CIs for IL-18 polymorphisms
and asthma were estimated using fixed- and random-effects models when appropriate. Heterogeneity and publication bias were
evaluated. We found that individuals carrying AC/CC genotype of −607C/A polymorphism were associated with an increased asthma
risk in recessive model (OR = 1.278; 95% CI, 1.073–1.522). However, no significant association was observed between −137G/C
polymorphism and asthma risk under different contrast models. There was no evidence of publication bias. The present meta-analysis
suggested that IL-18 −607C/A polymorphism in promoter region was associated with asthma risk. 相似文献
992.
993.
本文用高浓度的G418(800μg/ml)和低浓度的G418(200μg/ml)对包装细胞PLXSN/IL-2/PA317细胞进行40天的选择筛选培养,使其细胞呈稳定状态生长时,收集上清液转染NIH/3T3细胞,进行病毒滴度测定。试图在高选择标记的情况下筛选出高表达目的基因的包装细胞。实验结果表明:高、低浓度的G418对PLXSN/IL-2/PA317包装细胞的选择作用相同,即包装细胞的病毒滴度同选择标记物浓度无关。提示可用低浓度的G418来维持包装细胞的生命。 相似文献
994.
The interfering effects of copper, zinc, and cobalt on the uptake of mugineic acid-ferric complex were studied in barley ( Hordeum vulgare , cv. Minorimugi) grown in nutrient solution. Short-term uptake experiments of 3 h were performed utilizing both ionic and mugineic acid-complex forms of each metal at two different concentrations. Copper was most effective in decreasing iron uptake when added in an ionic form at either concentration. The inhibition order at higher concentrations followed Cu(II) > Zn(II) ≥ Co(II), Co(III), which is consistent with the stability constants of these metal complexes with mugineic acid. The displacement of iron from its mugineic acid complex by these metals is suggested as a probable explanation for the decreased iron uptake. The inhibitory effect of metal complexes with mugineic acid on iron uptake was only found in cases with higher concentrations of Cu(II) and Zn(II) complexes. Deformation of the specific iron transport system in the plasma membrane due to their adsorption may be responsible for this effect. 相似文献
995.
ACE2‐EPC‐EXs protect ageing ECs against hypoxia/reoxygenation‐induced injury through the miR‐18a/Nox2/ROS pathway 下载免费PDF全文
Xiaotang Ma Wenjun Wang Bin Zhao Yanfang Chen Can Chen Ji C. Bihl 《Journal of cellular and molecular medicine》2018,22(3):1873-1882
Oxidative stress is one of the mechanisms of ageing‐associated vascular dysfunction. Angiotensin‐converting enzyme 2 (ACE2) and microRNA (miR)‐18a have shown to be down‐regulated in ageing cells. Our previous study has shown that ACE2‐primed endothelial progenitor cells (ACE2‐EPCs) have protective effects on endothelial cells (ECs), which might be due to their released exosomes (EXs). Here, we aimed to investigate whether ACE2‐EPC‐EXs could attenuate hypoxia/reoxygenation (H/R)‐induced injury in ageing ECs through their carried miR‐18a. Young and angiotensin II‐induced ageing ECs were subjected to H/R and co‐cultured with vehicle (medium), EPC‐EXs, ACE2‐EPCs‐EXs, ACE2‐EPCs‐EXs + DX600 or ACE2‐EPCs‐EXs with miR‐18a deficiency (ACE2‐EPCs‐EXsanti‐miR‐18a). Results showed (1) ageing ECs displayed increased senescence, apoptosis and ROS production, but decreased ACE2 and miR‐18a expressions and tube formation ability; (2) under H/R condition, ageing ECs showed higher rate of apoptosis, ROS overproduction and nitric oxide reduction, up‐regulation of Nox2, down‐regulation of ACE2, miR‐18a and eNOS, and compromised tube formation ability; (3) compared with EPC‐EXs, ACE2‐EPC‐EXs had better efficiencies on protecting ECs from H/R‐induced changes; (4) The protective effects were less seen in ACE2‐EPCs‐EXs + DX600 and ACE2‐EPCs‐EXsanti‐miR‐18a groups. These data suggest that ACE‐EPCs‐EXs have better protective effects on H/R injury in ageing ECs which could be through their carried miR‐18a and subsequently down‐regulating the Nox2/ROS pathway. 相似文献
996.
Aleksandra Łukasiewicz Małgorzata Niśkiewicz Jacek Radwan 《Evolution; international journal of organic evolution》2020,74(8):1851-1855
Elaborate sexually selected ornaments and armaments are costly but increase the reproductive success of their bearers (usually males). It has been postulated that high-quality males can invest disproportionately more in such traits, making those traits honest signals of genetic quality. However, genes associated with such traits may have sexually antagonistic effects on fitness. Here, using a bulb mite Rhizoglyphus robini, a species in which a distinct dimorphism exists between males in the expression of a sexually selected weapon, we compare inbreeding and gender load between lines derived from armed fighters and unarmed scramblers. After four generations of sib-mating, inbreeding depression for female fitness was significantly lower in fighter-derived lines compared to scrambler-derived lines, suggesting that fighter males had significantly higher genetic quality. However, outbred females from fighter-derived lines had significantly lower fitness compared to outbred females from scrambler-derived lines, demonstrating significant gender load associated with the presence of a sexually selected male weapon. Our results imply that under outbreeding, genetic benefits of mating with bearers of elaborate sexually selected traits might be swamped by the costs of decreased fitness of female progeny due to sexually antagonistic effects. 相似文献
997.
Li Gao Yuanyuan Ma Xiting Li Liping Zhang Chi Zhang Qianying Chen Chuanjiang Zhao 《Journal of cellular biochemistry》2020,121(1):93-102
Porphyromonas gingivalis, as a major pathogen of periodontitis, could rapidly adhere to and invade host gingival epithelial cells (GECs) for the induction of infection. One ATP-binding cassette (ABC) transporter gene was found to be upregulated during this infection process, however, the molecular mechanisms remain unclear. In this study, we systemically investigated the messenger RNA level changes of all ABC transporter family genes in P. gingivalis while being internalized within GECs by real-time polymerase chain reaction. We identified that two ABC transporter genes, PG_RS04465 (PG1010) and PG_RS07320 (PG1665), were significantly increased in P. gingivalis after coculturing with GECs. Mutant strains with knockout (KO) of these two genes were generated by homogenous recombination. PG_RS04465 and PG_RS07320 KO mutants showed no change in the growth of bacteria per se. Knockdown of PG_RS07320, but not PG_RS04465, caused decreased endotoxin level in the bacteria. In contrast, both mutant strains showed decreased Arg- and Lys-gingipains activities, with significantly reduced adhesion and invasion capabilities. Secreted interleukin-1β (IL-1β) and IL-6 levels in GECs cocultured with PG_RS04465 or PG_RS07320 KO mutants were also decreased, whereas, only the cells cocultured with PG_RS07320 KO mutants showed significant decrease. In addition, virulence study using mouse revealed that both KO mutant strains infection caused less mouse death than wild-type strains, showing reduced virulence of two KO strains. These results indicated that ABC transporter genes PG_RS04465 and PG_RS07320 are positive regulators of the virulence of P. gingivalis. 相似文献
998.
Shihong Ma Dan Liu Wenhua Tan Botao Du Wei Liu Weijia Li Yufei Jiao 《Journal of cellular biochemistry》2020,121(5-6):3256-3265
Aberrant activation of the Hedgehog (Hh)/Gli pathway contributes to the tumorigenesis of several human cancers, including ovarian cancers. We investigated the function of SMO on cell growth, drug resistance, and invasive ability in A2780/DDP cells. Moreover, we also tested the levels of the downstream target genes of the Hh/Gli pathway in SMO short hairpin RNA (shRNA) lentivirus-infected A2780/DDP cells. Western blot analysis results revealed that the Hh/Gli pathway was activated in cisplatin-resistant A2780/DDP cells. After infection by SMO shRNA lentivirus, the colony formation rate and invasive rate of cisplatin-resistant A2780/DDP cells were decreased. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay showed that upon transfection with SMO shRNA, cell growth was decreased and drug sensitivity to cisplatin was upregulated. Moreover, interference with SMO decreased the expression of MMP-2, MMP-9, VEGF, and Snail in cisplatin-resistant cells. Thus, the Hh/Gli signaling pathway was aberrantly activated in A2780/DDP cells. The colony formation rate and invasive rate were decreased in SMO shRNA lentivirus–infected A2780/DDP cells. All results showed that inhibiting Hh/Gli signaling may negatively regulate the proliferation, invasion, and metastasis of cisplatin-resistant A2780/DDP cells, as well as increase the sensitivity of A2780/DDP to the chemotherapeutic drug of cisplatin. 相似文献
999.
The recently developed Hi-C technique has been widely applied to map genome-wide chromatin interactions. However, current methods for analyzing diploid Hi-C data cannot fully distinguish between homologous chromosomes. Consequently, the existing diploid Hi-C analyses are based on sparse and inaccurate allele-specific contact matrices, which might lead to incorrect modeling of diploid genome architecture. Here we present ASHIC, a hierarchical Bayesian framework to model allele-specific chromatin organizations in diploid genomes. We developed two models under the Bayesian framework: the Poisson-multinomial (ASHIC-PM) model and the zero-inflated Poisson-multinomial (ASHIC-ZIPM) model. The proposed ASHIC methods impute allele-specific contact maps from diploid Hi-C data and simultaneously infer allelic 3D structures. Through simulation studies, we demonstrated that ASHIC methods outperformed existing approaches, especially under low coverage and low SNP density conditions. Additionally, in the analyses of diploid Hi-C datasets in mouse and human, our ASHIC-ZIPM method produced fine-resolution diploid chromatin maps and 3D structures and provided insights into the allelic chromatin organizations and functions. To summarize, our work provides a statistically rigorous framework for investigating fine-scale allele-specific chromatin conformations. The ASHIC software is publicly available at https://github.com/wmalab/ASHIC. 相似文献
1000.
Identification of novel susceptibility loci for non‐syndromic cleft lip with or without cleft palate
Lan Ma Shu Lou Ziyue Miao Siyue Yao Xin Yu Shiyi Kan Guirong Zhu Fan Yang Chi Zhang Weibing Zhang Meilin Wang Lin Wang Yongchu Pan 《Journal of cellular and molecular medicine》2020,24(23):13669
Although several genome‐wide association studies (GWAS) of non‐syndromic cleft lip with or without cleft palate (NSCL/P) have been reported, more novel association signals are remained to be exploited. Here, we performed an in‐depth analysis of our previously published Chinese GWAS cohort study with replication in an extra dbGaP case‐parent trios and another in‐house Nanjing cohort, and finally identified five novel significant association signals (rs11119445: 3’ of SERTAD4, P = 6.44 × 10−14; rs227227 and rs12561877: intron of SYT14, P = 5.02 × 10−13 and 2.80 × 10−11, respectively; rs643118: intron of TRAF3IP3, P = 4.45 × 10−6; rs2095293: intron of NR6A1, P = 2.98 × 10−5). The mean (standard deviation) of the weighted genetic risk score (wGRS) from these SNPs was 1.83 (0.65) for NSCL/P cases and 1.58 (0.68) for controls, respectively (P = 2.67 × 10−16). Rs643118 was identified as a shared susceptible factor of NSCL/P among Asians and Europeans, while rs227227 may contribute to the risk of NSCL/P as well as NSCPO. In addition, sertad4 knockdown zebrafish models resulted in down‐regulation of sox2 and caused oedema around the heart and mandibular deficiency, compared with control embryos. Taken together, this study has improved our understanding of the genetic susceptibility to NSCL/P and provided further clues to its aetiology in the Chinese population. 相似文献