全文获取类型
收费全文 | 3043篇 |
免费 | 201篇 |
国内免费 | 7篇 |
专业分类
3251篇 |
出版年
2024年 | 5篇 |
2023年 | 11篇 |
2022年 | 42篇 |
2021年 | 53篇 |
2020年 | 43篇 |
2019年 | 63篇 |
2018年 | 98篇 |
2017年 | 60篇 |
2016年 | 124篇 |
2015年 | 163篇 |
2014年 | 189篇 |
2013年 | 204篇 |
2012年 | 268篇 |
2011年 | 310篇 |
2010年 | 171篇 |
2009年 | 148篇 |
2008年 | 182篇 |
2007年 | 193篇 |
2006年 | 135篇 |
2005年 | 119篇 |
2004年 | 111篇 |
2003年 | 91篇 |
2002年 | 87篇 |
2001年 | 62篇 |
2000年 | 55篇 |
1999年 | 40篇 |
1998年 | 27篇 |
1997年 | 29篇 |
1996年 | 16篇 |
1995年 | 16篇 |
1994年 | 12篇 |
1993年 | 12篇 |
1992年 | 10篇 |
1991年 | 10篇 |
1990年 | 14篇 |
1989年 | 19篇 |
1988年 | 12篇 |
1987年 | 7篇 |
1986年 | 6篇 |
1985年 | 4篇 |
1984年 | 7篇 |
1979年 | 5篇 |
1978年 | 2篇 |
1974年 | 1篇 |
1973年 | 1篇 |
1972年 | 2篇 |
1971年 | 3篇 |
1969年 | 2篇 |
1968年 | 1篇 |
1958年 | 1篇 |
排序方式: 共有3251条查询结果,搜索用时 15 毫秒
61.
Alexander Chi Pan Ma Guishan Fu Gerry Hobbs James S. Welsh Nam P. Nguyen Si Young Jang Jinrong Dai Jing Jin Ritsuko Komaki 《PloS one》2013,8(4)
Background
Helical tomotherapy (HT) and volumetric modulated arc therapy (VMAT) are both advanced techniques of delivering intensity-modulated radiotherapy (IMRT). Here, we conduct a study to compare HT and partial-arc VMAT in their ability to spare organs at risk (OARs) when stereotactic ablative radiotherapy (SABR) is delivered to treat centrally located early stage non-small-cell lung cancer or lung metastases.Methods
12 patients with centrally located lung lesions were randomly chosen. HT, 2 & 8 arc (Smart Arc, Pinnacle v9.0) plans were generated to deliver 70 Gy in 10 fractions to the planning target volume (PTV). Target and OAR dose parameters were compared. Each technique’s ability to meet dose constraints was further investigated.Results
HT and VMAT plans generated essentially equivalent PTV coverage and dose conformality indices, while a trend for improved dose homogeneity by increasing from 2 to 8 arcs was observed with VMAT. Increasing the number of arcs with VMAT also led to some improvement in OAR sparing. After normalizing to OAR dose constraints, HT was found to be superior to 2 or 8-arc VMAT for optimal OAR sparing (meeting all the dose constraints) (p = 0.0004). All dose constraints were met in HT plans. Increasing from 2 to 8 arcs could not help achieve optimal OAR sparing for 4 patients. 2/4 of them had 3 immediately adjacent structures.Conclusion
HT appears to be superior to VMAT in OAR sparing mainly in cases which require conformal dose avoidance of multiple immediately adjacent OARs. For such cases, increasing the number of arcs in VMAT cannot significantly improve OAR sparing. 相似文献62.
Jung Hwan Yoon Mi La Cho Yoo Jin Choi Ji Yeon Back Mi Kyung Park Suk Woo Lee Byung Joon Choi Hassan Ashktorab Duane T. Smoot Suk Woo Nam Jung Young Lee Won Sang Park 《Journal of cellular biochemistry》2013,114(8):1800-1809
Gastrokine 1 (GKN1) plays an important role in the gastric mucosal defense mechanism and also acts as a functional gastric tumor suppressor. In this study, we examined the effect of GKN1 on the expression of inflammatory mediators, including NF‐κB, COX‐2, and cytokines in GKN1‐transfected AGS cells and shGKN1‐transfected HFE‐145 cells. Lymphocyte migration and cell viability were also analyzed after treatment with GKN1 and inflammatory cytokines in AGS cells by transwell chemotaxis and an MTT assay, respectively. In GKN1‐transfected AGS cells, we observed inactivation and reduced expression of NF‐κB and COX‐2, whereas shGKN1‐transfected HFE‐145 cells showed activation and increased expression of NF‐κB and COX‐2. GKN1 expression induced production of inflammatory cytokines including IL‐8 and ‐17A, but decreased expression of IL‐6 and ‐10. We also found IL‐17A expression in 9 (13.6%) out of 166 gastric cancer tissues and its expression was closely associated with GKN1 expression. GKN1 also acted as a chemoattractant for the migration of Jurkat T cells and peripheral B lymphocytes in the transwell assay. In addition, GKN1 significantly reduced cell viability in both AGS and HFE‐145 cells. These data suggest that the GKN1 gene may inhibit progression of gastric epithelial cells to cancer cells by regulating NF‐κB signaling pathway and cytokine expression. J. Cell. Biochem. 114: 1800–1809, 2013. © 2013 Wiley Periodicals, Inc. 相似文献
63.
64.
Sohee Baek Nam Joo Kang Grzegorz M. Popowicz Marcelino Arciniega Sung Keun Jung Sanguine Byun Nu Ry Song Yong-Seok Heo Bo Yeon Kim Hyong Joo Lee Tad A. Holak Martin Augustin Ann M. Bode Robert Huber Zigang Dong Ki Won Lee 《Journal of molecular biology》2013,425(2):411-423
c-Jun NH2-terminal kinases (JNKs) and phosphatidylinositol 3-kinase (PI3-K) play critical roles in chronic diseases such as cancer, type II diabetes, and obesity. We describe here the binding of quercetagetin (3,3′,4′,5,6,7-hydroxyflavone), related flavonoids, and SP600125 to JNK1 and PI3-K by ATP-competitive and immobilized metal ion affinity-based fluorescence polarization assays and measure the effect of quercetagetin on JNK1 and PI3-K activities. Quercetagetin attenuated the phosphorylation of c-Jun and AKT, suppressed AP-1 and NF-κB promoter activities, and also reduced cell transformation. It attenuated tumor incidence and reduced tumor volumes in a two-stage skin carcinogenesis mouse model.Our crystallographic structure determination data show that quercetagetin binds to the ATP-binding site of JNK1. Notably, the interaction between Lys55, Asp169, and Glu73 of JNK1 and the catechol moiety of quercetagetin reorients the N-terminal lobe of JNK1, thereby improving compatibility of the ligand with its binding site. The results of a theoretical docking study suggest a binding mode of PI3-K with the hydroxyl groups of the catechol moiety forming hydrogen bonds with the side chains of Asp964 and Asp841 in the p110γ catalytic subunit. These interactions could contribute to the high inhibitory activity of quercetagetin against PI3-K. Our study suggests the potential use of quercetagetin in the prevention or therapy of cancer and other chronic diseases. 相似文献
65.
Krishna Nath Bong-Kwan Phee Suyeong Jeong Sun Yi Lee Yoshio Tateno Suleyman I. Allakhverdiev Choon-Hwan Lee Hong Gil Nam 《Photosynthesis research》2013,117(1-3):547-556
Photosynthetic complexes in the thylakoid membrane of plant leaves primarily function as energy-harvesting machinery during the growth period. However, leaves undergo developmental and functional transitions along aging and, at the senescence stage, these complexes become major sources for nutrients to be remobilized to other organs such as developing seeds. Here, we investigated age-dependent changes in the functions and compositions of photosynthetic complexes during natural leaf senescence in Arabidopsis thaliana. We found that Chl a/b ratios decreased during the natural leaf senescence along with decrease of the total chlorophyll content. The photosynthetic parameters measured by the chlorophyll fluorescence, photochemical efficiency (F v/F m) of photosystem II, non-photochemical quenching, and the electron transfer rate, showed a differential decline in the senescing part of the leaves. The CO2 assimilation rate and the activity of PSI activity measured from whole senescing leaves remained relatively intact until 28 days of leaf age but declined sharply thereafter. Examination of the behaviors of the individual components in the photosynthetic complex showed that the components on the whole are decreased, but again showed differential decline during leaf senescence. Notably, D1, a PSII reaction center protein, was almost not present but PsaA/B, a PSI reaction center protein is still remained at the senescence stage. Taken together, our results indicate that the compositions and structures of the photosynthetic complexes are differentially utilized at different stages of leaf, but the most dramatic change was observed at the senescence stage, possibly to comply with the physiological states of the senescence process. 相似文献
66.
In Jung Kim Hyeok-Jin Ko Tae-Wan Kim Ki Hyun Nam In-Geol Choi Kyoung Heon Kim 《Applied microbiology and biotechnology》2013,97(12):5381-5388
BsEXLX1 from Bacillus subtilis is the first discovered bacterial expansin as a structural homolog of a plant expansin, and it exhibited synergism with cellulase on the cellulose hydrolysis in a previous study. In this study, binding characteristics of BsEXLX1 were investigated using pretreated and untreated Miscanthus x giganteus in comparison with those of CtCBD3, a cellulose-binding domain from Clostridium thermocellum. The amounts of BsEXLX1 bound to cellulose-rich substrates were significantly lower than those of CtCBD3. However, the amounts of BsEXLX1 bound to lignin-rich substrates were much higher than those of CtCBD3. A binding competition assay between BsEXLX1 and CtCBD3 revealed that binding of BsEXLX1 to alkali lignin was not affected by the presence of CtCBD3. This preferential binding of BsEXLX1 to lignin could be related to root colonization in plants by bacteria, and the bacterial expansin could be used as a lignin blocker in the enzymatic hydrolysis of lignocellulose. 相似文献
67.
Genetic localization and in vivo characterization of a Monascus azaphilone pigment biosynthetic gene cluster 总被引:1,自引:0,他引:1
68.
Keun Sik Baik Yeoung Min Hwang Jong-Soon Choi Joseph Kwon Chi Nam Seong 《Antonie van Leeuwenhoek》2013,104(6):1143-1150
A motile, curved to twisted rod-shaped aerobic bacterium, designated strain 04SU4-PT, was isolated from freshwater collected from the Woopo wetland (Republic of Korea). Cells were observed to be Gram-stain negative, catalase negative and oxidase positive. The major fatty acids (>10 % of the total) were identified as C19:0 ω8c cyclo (24.6 %), C16:0 (24.3 %) and C18:1 ω7c (13.1 %). The DNA G+C content was determined to be 71.5 mol%. The major polar lipids were identified as phosphatidylglycerol, phosphatidylethanolamine, one unknown phospholipid and one unknown aminolipid. The major ubiquinone was determined to be Q-10. A phylogenetic tree based on 16S rRNA gene sequences showed that strain 04SU4-PT forms an evolutionary lineage within the genus Dongia and its nearest neighbour is Dongia mobilis LM22T (98.0 % sequence similarity). Genomic DNA–DNA hybridization of stain 04SU4-PT with D. mobilis LM22T showed relatedness of only 34.2 %. The phenotypic characteristics indicate the strain 04SU4-PT can be distinguished from the sole member of the genus Dongia. On the basis of the data presented in this study, strain 04SU4-PT represents a novel species, for which the name Dongia rigui is proposed. The type strain is 04SU4-PT (KCTC 23341T = JCM 17521T). 相似文献
69.
Youngjae Kim Jeeyeon Kim Jinsung Tae Bryan L. Roth Hyewhon Rhim Gyochang Keum Ghilsoo Nam Hyunah Choo 《Bioorganic & medicinal chemistry》2013,21(9):2568-2576
It has been reported that 5-HT7 receptors are promising targets of depression and neuropathic pain. 5-HT7 receptor antagonists have exhibited antidepressant-like profiles, while agonists have represented potential therapeutics for pain. In the course of our ongoing efforts to discover novel 5-HT7 modulators, we designed an arylpiperazine scaffold with a substituted biphenyl-2-ylmethyl group. A series of biphenyl-2-yl-arylpiperazinylmethanes were then prepared, which showed a broad spectrum of binding affinities to the 5-HT7 receptor depending upon the substituents attached to the biphenyl and aryl functionalities. Among those synthesized compounds, the compounds 1–24 and 1–26 showed the best binding affinities to the 5-HT7 receptor with Ki values of 43.0 and 46.0 nM, respectively. Structure–activity relationship study in conjunction with molecular docking study proposed that the 5-HT7 receptor might have two distinctive hydrophobic binding sites, one specific for aromatic 2-OCH3 substituents within the arylpiperazine and the other for biphenyl methoxy group. 相似文献
70.
Phuong-Thao Tran Van-Hai Hoang Shivaji A. Thorat Sung Eun Kim Jihyae Ann Yu Jin Chang Dong Woo Nam Hyundong Song Inhee Mook-Jung Jiyoun Lee Jeewoo Lee 《Bioorganic & medicinal chemistry》2013,21(13):3821-3830
In an effort to design inhibitors of human glutaminyl cyclase (QC), we have synthesized a library of N-aryl N-(5-methyl-1H-imidazol-1-yl)propyl thioureas and investigated the contribution of the aryl region of these compounds to their structure–activity relationships as cyclase inhibitors. Our design was guided by the proposed binding mode of the preferred substrate for the cyclase. In this series, compound 52 was identified as the most potent QC inhibitor with an IC50 value of 58 nM, which was two-fold more potent than the previously reported lead 2. Compound 52 is a most promising candidate for future evaluation to monitor its ability to reduce the formation of pGlu-Aβ and Aβ plaques in cells and transgenic animals. 相似文献