全文获取类型
收费全文 | 29338篇 |
免费 | 2157篇 |
国内免费 | 1675篇 |
专业分类
33170篇 |
出版年
2024年 | 64篇 |
2023年 | 346篇 |
2022年 | 837篇 |
2021年 | 1412篇 |
2020年 | 965篇 |
2019年 | 1200篇 |
2018年 | 1174篇 |
2017年 | 834篇 |
2016年 | 1240篇 |
2015年 | 1902篇 |
2014年 | 2159篇 |
2013年 | 2303篇 |
2012年 | 2638篇 |
2011年 | 2310篇 |
2010年 | 1469篇 |
2009年 | 1259篇 |
2008年 | 1517篇 |
2007年 | 1351篇 |
2006年 | 1188篇 |
2005年 | 993篇 |
2004年 | 792篇 |
2003年 | 703篇 |
2002年 | 537篇 |
2001年 | 483篇 |
2000年 | 382篇 |
1999年 | 411篇 |
1998年 | 244篇 |
1997年 | 266篇 |
1996年 | 253篇 |
1995年 | 214篇 |
1994年 | 218篇 |
1993年 | 151篇 |
1992年 | 216篇 |
1991年 | 188篇 |
1990年 | 131篇 |
1989年 | 107篇 |
1988年 | 79篇 |
1987年 | 109篇 |
1986年 | 82篇 |
1985年 | 70篇 |
1984年 | 52篇 |
1983年 | 36篇 |
1982年 | 36篇 |
1981年 | 26篇 |
1980年 | 21篇 |
1979年 | 25篇 |
1978年 | 17篇 |
1975年 | 21篇 |
1974年 | 18篇 |
1972年 | 17篇 |
排序方式: 共有10000条查询结果,搜索用时 0 毫秒
991.
Fang Zeng Wei Qin Yue Yang Danhua Zhang Jixin Liu Guangyu Zhou Jinbo Sun Shengfeng Lu Yong Tang Yuan Chen Lei Lan Shuguang Yu Ying Li Xin Gao Qiyong Gong Jie Tian Fanrong Liang 《PloS one》2013,8(7)
Background and Aims
Brain dysfunction in functional dyspepsia (FD) has been identified by multiple neuroimaging studies. This study aims to investigate the regional gray matter density (GMD) changes in meal-related FD patients and their correlations with clinical variables, and to explore the possible influence of the emotional state on FD patients’s brain structures.Methods
Fifty meal-related FD patients and forty healthy subjects (HS) were included and underwent a structural magnetic resonance imaging scan. Voxel-based morphometry analysis was employed to identify the cerebral structure alterations in meal-related FD patients. Regional GMD changes'' correlations with the symptoms and their durations, respectively, have been analyzed.Results
Compared to the HS, the meal-related FD patients showed a decreased GMD in the bilateral precentral gyrus, medial prefrontal cortex (MPFC), anterior cingulate cortex (ACC) and midcingulate cortex (MCC), left orbitofrontal cortex (OFC) and right insula (p<0.05, FWE Corrected, Cluster size>50). After controlling for anxiety and depression, the meal-related FD patients showed a decreased GMD in the bilateral middle frontal gyrus, left MCC, right precentral gyrus and insula (p<0.05, FWE Corrected, Cluster size>50). Before controlling psychological factors, the GMD decreases in the ACC were negatively associated with the symptom scores of the Nepean Dyspepsia Index (NDI) (r = −0.354, p = 0.048, Bonferroni correction) and the duration of FD (r = −0.398, p = 0.02, Bonferroni correction) respectively.Conclusions
The regional GMD of meal-related FD patients, especially in the regions of the homeostatic afferent processing network significantly differed from that of the HS, and the psychological factors might be one of the essential factors significantly affecting the regional brain structure of meal-related FD patients. 相似文献992.
James L. Trevaskis Christine M. Mack Chengzao Sun Christopher J. Soares Lawrence J. D’Souza Odile E. Levy Diane Y. Lewis Carolyn M. Jodka Krystyna Tatarkiewicz Bronislava Gedulin Swati Gupta Carrie Wittmer Michael Hanley Bruce Forood David G. Parkes Soumitra S. Ghosh 《PloS one》2013,8(10)
Combination therapy is being increasingly used as a treatment paradigm for metabolic diseases such as diabetes and obesity. In the peptide therapeutics realm, recent work has highlighted the therapeutic potential of chimeric peptides that act on two distinct receptors, thereby harnessing parallel complementary mechanisms to induce additive or synergistic benefit compared to monotherapy. Here, we extend this hypothesis by linking a known anti-diabetic peptide with an anti-obesity peptide into a novel peptide hybrid, which we termed a phybrid. We report on the synthesis and biological activity of two such phybrids (AC164204 and AC164209), comprised of a glucagon-like peptide-1 receptor (GLP1-R) agonist, and exenatide analog, AC3082, covalently linked to a second generation amylin analog, davalintide. Both molecules acted as full agonists at their cognate receptors in vitro, albeit with reduced potency at the calcitonin receptor indicating slightly perturbed amylin agonism. In obese diabetic Lepob/Lep
ob mice sustained infusion of AC164204 and AC164209 reduced glucose and glycated haemoglobin (HbA1c) equivalently but induced greater weight loss relative to exenatide administration alone. Weight loss was similar to that induced by combined administration of exenatide and davalintide. In diet-induced obese rats, both phybrids dose-dependently reduced food intake and body weight to a greater extent than exenatide or davalintide alone, and equal to co-infusion of exenatide and davalintide. Phybrid-mediated and exenatide + davalintide-mediated weight loss was associated with reduced adiposity and preservation of lean mass. These data are the first to provide in vivo proof-of-concept for multi-pathway targeting in metabolic disease via a peptide hybrid, demonstrating that this approach is as effective as co-administration of individual peptides. 相似文献
993.
The
Drosophila
compound eye is a large sensory organ that places a high demand on oxygen supplied by the tracheal system. Although the development and function of the
Drosophila
visual system has been extensively studied, the development and contribution of its tracheal system has not been systematically examined. To address this issue, we studied the tracheal patterns and developmental process in the
Drosophila
visual system. We found that the retinal tracheae are derived from air sacs in the head, and the ingrowth of retinal trachea begin at mid-pupal stage. The tracheal development has three stages. First, the air sacs form near the optic lobe in 42-47% of pupal development (pd). Second, in 47-52% pd, air sacs extend branches along the base of the retina following a posterior-to-anterior direction and further form the tracheal network under the fenestrated membrane (TNUFM). Third, the TNUFM extend fine branches into the retina following a proximal-to-distal direction after 60% pd. Furthermore, we found that the trachea extension in both retina and TNUFM are dependent on the FGF(Bnl)/FGFR(Btl) signaling. Our results also provided strong evidence that the photoreceptors are the source of the Bnl ligand to guide the trachea ingrowth. Our work is the first systematic study of the tracheal development in the visual system, and also the first study demonstrating the interactions of two well-studied systems: the eye and trachea. 相似文献
994.
Jiqing Zhang Changjian Xia Canxing Duan Suli Sun Xiaoming Wang Xiaofei Wu Zhendong Zhu 《PloS one》2013,8(7)
Resistance to Phytophthora sojae isolate PsMC1 was evaluated in 102 F2∶3 families derived from a cross between the resistant soybean cultivar Wandou 15 and the susceptible cultivar Williams and genotyped using simple sequence repeat (SSR) markers. The segregation ratio of resistant, segregating, and susceptible phenotypes in the population suggested that the resistance in Wandou 15 was dominant and monogenic. Twenty-six polymorphic SSR markers were identified on soybean chromosome 17 (Molecular linkage group D2; MLG D2), which were linked to the resistance gene based on bulked segregation analysis (BSA). Markers Sattwd15-24/25 and Sattwd15-47 flanked the resistance gene at a distance of 0.5 cM and 0.8 cM, respectively. Two cosegregating markers, Sattwd15-28 and Sattwd15-32, were also screened in this region. This is the first Rps resistance gene mapped on chromosome 17, which is designated as Rps10. Eight putative genes were found in the mapped region between markers Sattwd15-24/25 and Sattwd15-47. Among them, two candidate genes encoding serine/threonine (Ser/Thr) protein kinases in Wandou 15 and Williams were identified and sequenced. And the differences in genomic sequence and the putative amino acid sequence, respectively, were identified within each candidate gene between Wandou 15 and Williams. This novel gene Rps10 and the linked markers should be useful in developing soybean cultivars with durable resistance to P. sojae. 相似文献
995.
Wei Wang Mei Zhang Weimin Sun Shanmin Yang Ying Su Hengshan Zhang Chaomei Liu Xinfeng Li Ling Lin Sunghee Kim Paul Okunieff Zhenhuan Zhang Lurong Zhang 《PloS one》2013,8(10)
Most human pancreatic cancer cells are resistant to tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis. However, the mechanisms by which pancreatic cancer cells utilize their extracellular molecules to counteract the proapoptotic signaling mediated by the TNF family are largely unknown. In this study, we demonstrate for the first time that DcR3, a secreted decoy receptor that malignant pancreatic cancer cells express at a high level, acts as an extracellular antiapoptotic molecule by binding to TRAIL and counteracting its death-promoting function. The reduction of DcR3 with siRNA unmasked TRAIL and greatly enhanced TRAIL-induced apoptosis. Gemcitabine, a first-line drug for pancreatic cancer, also reduced the level of DcR3. The addition of DcR3 siRNA further enhanced gemcitabine-induced apoptosis. Notably, our in vivo study demonstrated that the therapeutic effect of gemcitabine could be enhanced via further reduction of DcR3, suggesting that downregulation of DcR3 in tumor cells could tip the balance of pancreatic cells towards apoptosis and potentially serve as a new strategy for pancreatic cancer therapy. 相似文献
996.
Ran Liu Miao Yang Yanli Meng Juan Liao Jingyi Sheng Yuepu Pu Lihong Yin Sun Jung Kim 《PloS one》2013,8(10)
Recent studies have demonstrated the possible function of miR-139-5p in tumorigenesis. However, the exact mechanism of miR-139-5p in cancer remains unclear. In this study, the association of miR-139-5p expression with esophageal squamous cell carcinoma (ESCC) was evaluated in 106 pairs of esophageal cancer and adjacent non-cancerous tissue from ESCC patients. The tumor suppressive features of miR-139-5p were measured by evaluating cell proliferation and cell cycle state, migratory activity and invasion capability, as well as apoptosis. Luciferase reporter assay and Western blot analysis were performed to determine the target gene regulated by miR-139-5p. The mRNA level of NR5A2, the target gene of miR-139-5p, was determined in ESCC patients. Results showed that reduced miR-139-5p level was associated with lymph node metastases of ESCC. MiR-139-5p was investigated to induce cell cycle arrest in the G0/G1 phase and to suppress the invasive capability of esophageal carcinoma cells by targeting the 3′UTR of oncogenic NR5A2. Cyclin E1 and MMP9 were confirmed to participate in cell cycle arrest and invasive suppression induced by NR5A2, respectively. Pearson correlation analysis further confirmed the significantly negative correlation between miR-139-5p and NR5A2 expression. The results suggest that miR-139-5p exerts a growth- and invasiveness-suppressing function in human ESCCs, which demonstrates that miR-139-5p is a potential biomarker for early diagnosis and prognosis and is a therapeutic target for ESCC. 相似文献
997.
Chunchao Wang Qiang Wei Kang Zhang Ling Wang Fengxia Liu Linna Zhao Yuanjun Tan Chao Di Hong Yan Jingjuan Yu Chuanqing Sun Wenqiong J. Chen Wenying Xu Zhen Su 《PloS one》2013,8(12)
Rice SPX domain gene, OsSPX1, plays an important role in the phosphate (Pi) signaling network. Our previous work showed that constitutive overexpression of OsSPX1 in tobacco and Arabidopsis plants improved cold tolerance while also decreasing total leaf Pi. In the present study, we generated rice antisense and sense transgenic lines of OsSPX1 and found that down-regulation of OsSPX1 caused high sensitivity to cold and oxidative stresses in rice seedlings. Compared to wild-type and OsSPX1-sense transgenic lines, more hydrogen peroxide accumulated in seedling leaves of OsSPX1-antisense transgenic lines for controls, cold and methyl viologen (MV) treatments. Glutathione as a ROS scavenger could protect the antisense transgenic lines from cold and MV stress. Rice whole genome GeneChip analysis showed that some oxidative-stress marker genes (e.g. glutathione S-transferase and P450s) and Pi-signaling pathway related genes (e.g. OsPHO2) were significantly down-regulated by the antisense of OsSPX1. The microarray results were validated by real-time RT-PCR. Our study indicated that OsSPX1 may be involved in cross-talks between oxidative stress, cold stress and phosphate homeostasis in rice seedling leaves. 相似文献
998.
Xiao Sun Adam D. Kay Hongzhang Kang Gaston E. Small Guofang Liu Xuan Zhou Shan Yin Chunjiang Liu 《PloS one》2013,8(11)
Using samples from eastern China (c. 25 – 41° N and 99 – 123° E) and from a common garden experiment, we investigate how Mg concentration varies with climate across multiple trophic levels. In soils, plant tissue (Oriental oak leaves and acorns), and a specialist acorn predator (the weevil Curculio davidi), Mg concentration increased significantly with different slopes from south to north, and generally decreased with both mean annual temperature (MAT) and precipitation (MAP). In addition, soil, leaf, acorn and weevil Mg showed different strengths of association and sensitivity with climatic factors, suggesting that distinct mechanisms may drive patterns of Mg variation at different trophic levels. Our findings provide a first step toward determining whether anticipated changes in temperature and precipitation due to climate change will have important consequences for the bioavailability and distribution of Mg in food chain. 相似文献
999.
1000.
Xiang Qian Lao Ignatius Tak Sun Yu Dennis Kin Kwok Au Yuk Lan Chiu Claudie Chiu Yi Wong Tze Wai Wong 《PloS one》2013,8(8)