全文获取类型
收费全文 | 2317篇 |
免费 | 165篇 |
国内免费 | 112篇 |
出版年
2024年 | 5篇 |
2023年 | 22篇 |
2022年 | 66篇 |
2021年 | 122篇 |
2020年 | 88篇 |
2019年 | 83篇 |
2018年 | 75篇 |
2017年 | 64篇 |
2016年 | 107篇 |
2015年 | 136篇 |
2014年 | 154篇 |
2013年 | 191篇 |
2012年 | 194篇 |
2011年 | 179篇 |
2010年 | 114篇 |
2009年 | 90篇 |
2008年 | 114篇 |
2007年 | 109篇 |
2006年 | 90篇 |
2005年 | 68篇 |
2004年 | 64篇 |
2003年 | 57篇 |
2002年 | 61篇 |
2001年 | 39篇 |
2000年 | 37篇 |
1999年 | 30篇 |
1998年 | 13篇 |
1997年 | 15篇 |
1996年 | 17篇 |
1995年 | 17篇 |
1994年 | 11篇 |
1993年 | 12篇 |
1992年 | 23篇 |
1991年 | 17篇 |
1990年 | 14篇 |
1989年 | 9篇 |
1988年 | 13篇 |
1987年 | 11篇 |
1986年 | 12篇 |
1985年 | 5篇 |
1984年 | 4篇 |
1983年 | 5篇 |
1982年 | 4篇 |
1980年 | 5篇 |
1975年 | 4篇 |
1973年 | 4篇 |
1971年 | 3篇 |
1969年 | 3篇 |
1968年 | 2篇 |
1967年 | 2篇 |
排序方式: 共有2594条查询结果,搜索用时 31 毫秒
111.
112.
Jianhui Ji Ding Tang Mo Wang Yafei Li Lei Zhang Kejian Wang Ming Li Zhukuan Cheng 《Chromosoma》2013,122(5):363-376
Mre11, a conserved protein found in organisms ranging from yeast to multicellular organisms, is required for normal meiotic recombination. Mre11 interacts with Rad50 and Nbs1/Xrs2 to form a complex (MRN/X) that participates in double-strand break (DSB) ends processing. In this study, we silenced the MRE11 gene in rice and detailed its function using molecular and cytological methods. The OsMRE11-deficient plants exhibited normal vegetative growth but could not set seed. Cytological analysis indicated that in the OsMRE11-deficient plants, homologous pairing was totally inhibited, and the chromosomes were completely entangled as a formation of multivalents at metaphase I, leading to the consequence of serious chromosome fragmentation during anaphase I. Immunofluorescence studies further demonstrated that OsMRE11 is required for homologous synapsis and DSB processing but is dispensable for meiotic DSB formation. We found that OsMRE11 protein was located on meiotic chromosomes from interphase to late pachytene. This protein showed normal localization in zep1, Oscom1 and Osmer3, as well as in OsSPO11-1 RNAi plants, but not in pair2 and pair3 mutants. Taken together, our results provide evidence that OsMRE11 performs a function essential for maintaining the normal HR process and inhibiting non-homologous recombination during meiosis. 相似文献
113.
Mo Liu Jianguang Wang Hongzhang Huang Jingsong Hou Bin Zhang Anxun Wang 《Biochemical and biophysical research communications》2013
Although many researches have been undertaken to disclose the mechanisms of chemoresistance, the mechanisms remain unclear. The aim of this study is to elucidate the role of miR-181a–Twist1 pathway in the chemoresistance of tongue squamous cell carcinoma (TSCC). We found that cisplatin-induced chemoresistance in TSCC cell lines underwent EMT (epithelial–mesenchymal transition) and was accompanied by enhancing metastatic potential (migration and invasion in vitro), miR-181a downregulation and Twist1 upregulation. Functional analyses indicated that miR-181a reversed chemoresistance, inhibited EMT and metastatic potential in TSCC cells. Twist1 was confirmed as a direct miR-181a target gene by luciferase reporter gene assays. Twist1 knockdown by siRNA led to a reversal of the chemoresistance, inhibited EMT and metastatic potential in TSCC cells. Our study demonstrates that miR-181a–Twist1 pathway may play an important role in the development of cisplatin-chemoresistance, with EMT and an increase the metastatic potential of TSCC cells. 相似文献
114.
Bo Kang Zhongchen Zhang Lingling Wang Libin Zheng Weihua Mao Meifei Li Yunrong Wu Ping Wu Xiaorong Mo 《The Plant journal : for cell and molecular biology》2013,74(1):86-97
Auxin plays a pivotal role in many facets of plant development. It acts by inducing the interaction between auxin‐responsive [auxin (AUX)/indole‐3‐acetic acid (IAA)] proteins and the ubiquitin protein ligase SCFTIR to promote the degradation of the AUX/IAA proteins. Other cofactors and chaperones that participate in auxin signaling remain to be identified. Here, we characterized rice (Oryza sativa) plants with mutations in a cyclophilin gene (OsCYP2). cyp2 mutants showed defects in auxin responses and exhibited a variety of auxin‐related growth defects in the root. In cyp2 mutants, lateral root initiation was blocked after nuclear migration but before the first anticlinal division of the pericycle cell. Yeast two‐hybrid and in vitro pull‐down results revealed an association between OsCYP2 and the co‐chaperone Suppressor of G2 allele of skp1 (OsSGT1). Luciferase complementation imaging assays further supported this interaction. Similar to previous findings in an Arabidopsis thaliana SGT1 mutant (atsgt1b), degradation of AUX/IAA proteins was retarded in cyp2 mutants treated with exogenous 1‐naphthylacetic acid. Our results suggest that OsCYP2 participates in auxin signal transduction by interacting with OsSGT1. 相似文献
115.
Xiao-long Tang Feng Yue Jian-zheng He Ning-bo Wang Ming Ma Jia-run Mo Qiang Chen 《Zoology (Jena, Germany)》2013,116(6):331-335
A viviparous lizard, Eremias multiocellata, was used to investigate the possible sexual and ontogenetic effects on selected body temperature, thermal tolerance range and the thermal dependence of locomotor performance. We show that adults are sexually dimorphic and males have larger bodies and heads than females. Adults selected higher body temperatures (34.5 vs. 32.4 °C) and could tolerate a broader range of body temperatures (8.1–46.8 vs. 9.1–43.1 °C) than juveniles. The sprint speed and maximum sprint distance increased with temperature from 21 °C to 33 °C, but decreased at 36 °C and 39 °C in both juveniles and adults. Adults ran faster and longer than juveniles at each tested temperature. Adult locomotor performance was not correlated with snout–vent length (SVL) or sex, and sprint speed was positively correlated with hindlimb length. Juvenile locomotor performance was positively correlated with both SVL and hindlimb length. The ontogenetic variation in selected body temperature, thermal tolerance and locomotor performance in E. multiocellata suggests that the effects of morphology on temperature selection and locomotor performance vary at different ontogenetic stages. 相似文献
116.
The melanocortin-4 receptor (MC4R) is a G protein-coupled receptor that plays an essential role in regulating energy homeostasis. Defects in MC4R are the most common monogenic form of obesity, with about 170 distinct mutations identified in human. In addition to the conventional Gs-stimulated adenylyl cyclase pathway, it has been recently demonstrated that MC4R also activates mitogen-activated protein kinases, extracellular signal-regulated kinases 1 and 2 (ERK1/2). Herein, we investigated the potential of four MC4R ligands that are inverse agonists at the Gs-cAMP signaling pathway, including agouti-related peptide (AgRP), MCL0020, Ipsen 5i and ML00253764, to regulate ERK1/2 activation (pERK1/2) in wild type and six naturally occurring constitutively active mutant (CAM) MC4Rs. We showed that these four inverse agonists acted as agonists for the ERK1/2 signaling cascade in wild type and CAM MC4Rs. Three mutants (P230L, L250Q and F280L) had significantly increased pERK1/2 level upon stimulation with all four inverse agonists, with maximal induction ranging from 1.6 to 4.2-fold. D146N had significantly increased pERK1/2 level upon stimulation with AgRP, MCL0020 or ML00253764, but not Ipsen 5i. The pERK1/2 levels of H76R and S127L were significantly increased only upon stimulation with AgRP or MCL0020. In summary, our studies demonstrated for the first time that MC4R inverse agonists at the Gs-cAMP pathway could serve as agonists in the MAPK pathway. These results suggested that there were multiple activation states of MC4R with ligand-specific and/or mutant-specific conformations capable of differentially coupling the MC4R to distinct signaling pathways. 相似文献
117.
C-W Fan T Chen Y-N Shang Y-Z Gu S-L Zhang R Lu S-R OuYang X Zhou Y Li W-T Meng J-K Hu Y Lu X-F Sun H Bu Z-G Zhou X-M Mo 《Cell death & disease》2013,4(10):e828
Accumulating evidence indicates that cancer-initiating cells (CICs) are responsible for cancer initiation, relapse, and metastasis. Colorectal carcinoma (CRC) is typically classified into proximal colon, distal colon, and rectal cancer. The gradual changes in CRC molecular features within the bowel may have considerable implications in colon and rectal CICs. Unfortunately, limited information is available on CICs derived from rectal cancer, although colon CICs have been described. Here we identified rectal CICs (R-CICs) that possess differentiation potential in tumors derived from patients with rectal adenocarcinoma. The R-CICs carried both CD44 and CD54 surface markers, while R-CICs and their immediate progenies carried potential epithelial–mesenchymal transition characteristics. These R-CICs generated tumors similar to their tumor of origin when injected into immunodeficient mice, differentiated into rectal epithelial cells in vitro, and were capable of self-renewal both in vitro and in vivo. More importantly, subpopulations of R-CICs resisted both 5-fluorouracil/calcium folinate/oxaliplatin (FolFox) and cetuximab treatment, which are the most common therapeutic regimens used for patients with advanced or metastatic rectal cancer. Thus, the identification, expansion, and properties of R-CICs provide an ideal cellular model to further investigate tumor progression and determine therapeutic resistance in these patients. 相似文献
118.
Xue Qin Yan Deng Zhi-Yu Zeng Qi-Liu Peng Xiu-Li Huang Cui-Ju Mo Shan Li Jin-Min Zhao 《PloS one》2013,8(8)
Myeloperoxidase (MPO) is a metabolic/oxidative lysosomal enzyme secreted by reactive neutrophils at the sites of inflamed organs and tissues during phagocytosis. MPO has been either directly or indirectly linked to neoplasia, which is a well-established risk factor for many types of cancer. A large number of studies have reported the role of MPO G-463A polymorphism regarding breast-cancer risk. However, the published findings are inconsistent. Therefore, we conducted a meta-analysis to determine more precise estimations for the relationship. Eligible studies were identified by searching several electronic databases for relevant reports published before June 2012. According to the inclusion criteria and exclusion criteria, a total of five eligible studies were included in the pooled analyses. When the five eligible studies concerning MPO G-463A polymorphism were pooled into this meta-analysis, there was no evidence found for a significant association between MPO G-463A polymorphism and breast-cancer risk in any genetic model. We also categorized by ethnicity (Caucasian or Asian) for subgroup analysis; according to this subgroup analysis, we found no significant association between MPO G-463A polymorphism and breast-cancer risk in any genetic model. However, in the stratified analysis for the premenopausal group, women carrying the AA genotype were found to have a significantly reduced risk (OR = 0.56, 95% CI 0.34–0.94, p = 0.027). Under the recessive model, there was a significant association between MPO G-463A polymorphism and breast-cancer risk (OR = 0.57, 95% CI 0.34–0.93, p = 0.025). We conclude that MPO-G463A polymorphism might not be a good predictor of breast-cancer risk, though menopausal status modified women’s risk of developing breast cancer. 相似文献
119.
Yunjuan Gu Chunfang Wang Ying Zheng Xuhong Hou Yifei Mo Weihui Yu Lei Zhang Cheng Hu Hairong Nan Lei Chen Jie Li Yuxiang Liu Zhezhou Huang Ming Han Yuqian Bao Weijian Zhong Weiping Jia 《PloS one》2013,8(1)
Aim
The aim was to investigate the association between human insulin and cancer incidence and mortality in Chinese patients with type 2 diabetes.Methods
We recruited 8,774 insulin-naïve diabetes patients from the Shanghai Diabetes Registry (SDR). The follow-up rate was 85.4%. All subjects were divided into the insulin use cohort (n = 3,639) and the non-insulin use cohort (n = 5,135). The primary outcome was the first diagnosis of any cancer. The secondary outcome was all-cause mortality. Cox proportional hazards model was used to estimate the relative risk (RR) of cancer and mortality.Results
We observed 98 cancer events in the insulin use cohort and 170 in the non-insulin use cohort. Cancer incidence rates were 78.6 and 74.3 per 10,000 patients per year in the insulin users and the non-insulin users, respectively. No significant difference in cancer risk was observed between the two cohorts (adjusted RR = 1.20, 95% CI 0.89–1.62, P = 0.228). Regarding site-specific cancers, only the risk of liver cancer was significantly higher in the insulin users compared to that in the non-insulin users (adjusted RR = 2.84, 95% CI 1.12–7.17, P = 0.028). The risks of overall mortality (adjusted RR = 1.89, 95% CI 1.47–2.43, P<0.0001) and death from cancer (adjusted RR = 2.16, 95% CI 1.39–3.35, P = 0.001) were all significantly higher in the insulin users than in the non-insulin users.Conclusion
There was no excess risk of overall cancer in patients with type 2 diabetes who were treated with human insulin. However, a significantly higher risk of liver cancer was found in these patients. Moreover, insulin users showed higher risks of overall and cancer mortality. Considering that individuals treated with insulin were more likely to be advanced diabetic patients, caution should be used in interpreting these results. 相似文献120.
Using the event-related optical signal (EROS) technique, this study investigated the dynamics of semantic brain activation during sentence comprehension. Participants read sentences constituent-by-constituent and made a semantic judgment at the end of each sentence. The EROSs were recorded simultaneously with ERPs and time-locked to expected or unexpected sentence-final target words. The unexpected words evoked a larger N400 and a late positivity than the expected ones. Critically, the EROS results revealed activations first in the left posterior middle temporal gyrus (LpMTG) between 128 and 192 ms, then in the left anterior inferior frontal gyrus (LaIFG), the left middle frontal gyrus (LMFG), and the LpMTG in the N400 time window, and finally in the left posterior inferior frontal gyrus (LpIFG) between 832 and 864 ms. Also, expected words elicited greater activation than unexpected words in the left anterior temporal lobe (LATL) between 192 and 256 ms. These results suggest that the early lexical-semantic retrieval reflected by the LpMTG activation is followed by two different semantic integration processes: a relatively rapid and transient integration in the LATL and a relatively slow but enduring integration in the LaIFG/LMFG and the LpMTG. The late activation in the LpIFG, however, may reflect cognitive control. 相似文献