全文获取类型
收费全文 | 8157篇 |
免费 | 531篇 |
国内免费 | 4篇 |
专业分类
8692篇 |
出版年
2024年 | 9篇 |
2023年 | 23篇 |
2022年 | 105篇 |
2021年 | 157篇 |
2020年 | 87篇 |
2019年 | 119篇 |
2018年 | 163篇 |
2017年 | 156篇 |
2016年 | 226篇 |
2015年 | 429篇 |
2014年 | 432篇 |
2013年 | 512篇 |
2012年 | 720篇 |
2011年 | 625篇 |
2010年 | 398篇 |
2009年 | 366篇 |
2008年 | 484篇 |
2007年 | 508篇 |
2006年 | 454篇 |
2005年 | 392篇 |
2004年 | 384篇 |
2003年 | 325篇 |
2002年 | 285篇 |
2001年 | 249篇 |
2000年 | 230篇 |
1999年 | 165篇 |
1998年 | 62篇 |
1997年 | 54篇 |
1996年 | 34篇 |
1995年 | 34篇 |
1994年 | 21篇 |
1993年 | 21篇 |
1992年 | 40篇 |
1991年 | 48篇 |
1990年 | 39篇 |
1989年 | 46篇 |
1988年 | 35篇 |
1987年 | 25篇 |
1986年 | 25篇 |
1985年 | 31篇 |
1984年 | 20篇 |
1983年 | 17篇 |
1981年 | 9篇 |
1979年 | 11篇 |
1978年 | 13篇 |
1977年 | 10篇 |
1974年 | 12篇 |
1973年 | 14篇 |
1972年 | 11篇 |
1971年 | 7篇 |
排序方式: 共有8692条查询结果,搜索用时 15 毫秒
91.
92.
Joo-Hyun Kim Eun-Hyang Lee Hye-jeong Park Eui-Kyun Park Tae-Geon Kwon Hong-In Shin Je-Yoel Cho 《Molecules and cells》2013,35(6):543-549
Adult human dental pulp stem cells (hDPSCs) are a unique population of precursor cells those are isolated from postnatal dental pulp and have the ability to differentiate into a variety of cell types utilized for the formation of a reparative dentin-like complex. Using LC-MS/MS proteomics approaches, we identified the proteins secreted from the differentiating hDPSCs in mineralization media. Lysyl oxidase-like 2 (LOXL2) was identified as a protein that was down-regulated in the hDPSCs that differentiate into odontoblast-like cells. The role of LOXL2 has not been studied in dental pulp stem cells. LOXL2 mRNA levels were reduced in differentiating hDPSCs, whereas the levels of other LOX family members including LOX, LOXL1, LOXL3, and LOXL4, are increased. The protein expression and secretion levels of LOXL2 were also decreased during odontogenic differentiation. Recombinant LOXL2 protein treatment to hDPSCs resulted in a dose-dependent decrease in the early differentiation and the mineralization accompanying with the lower levels of odontogenic markers such as DSPP, DMP-1 and ALP. These results suggest that LOXL2 has a negative effect on the differentiation of hDPSCs and blocking LOXL2 can promote the hDPSC differentiation to odontoblasts. 相似文献
93.
Seung Hyeok Seok Jong-Ik Heo Ji-Hye Hwang Yi-Rang Na Jang-Hyuk Yun Eun Hui Lee Jong-Wan Park Chung-Hyun Cho 《Molecules and cells》2013,35(6):550-556
The angiopoietin/Tie2 system is an important regulator of angiogenesis and inflammation. In addition to its functions in endothelial cells, Tie2 expression on non-endothelial cells allows for angiopoietin ligands to stimulate the cells. Although Ang1 is a strong Tie2 receptor agonist, little is known regarding the effect of Ang1 on non-endothelial cells, such as monocytes and macrophages. In this study, we found that Ang1 functionally binds to and stimulates monocytes via p38 and Erk1/2 phosphorylation. Ang1-mediated monocyte stimulation is associated with proinflammatory cytokine TNF-α expression. We also determined that Ang1 switched macrophage differentiation toward a pro-inflammatory phenotype, even in the presence of an anti-inflammatory mediator. These findings suggest that Ang1 plays a role in stimulating pro-inflammatory responses and could provide a new strategy by which to manage inflammatory responses. 相似文献
94.
95.
Background
Protein-protein interactions (PPIs) play a key role in understanding the mechanisms of cellular processes. The availability of interactome data has catalyzed the development of computational approaches to elucidate functional behaviors of proteins on a system level. Gene Ontology (GO) and its annotations are a significant resource for functional characterization of proteins. Because of wide coverage, GO data have often been adopted as a benchmark for protein function prediction on the genomic scale.Results
We propose a computational approach, called M-Finder, for functional association pattern mining. This method employs semantic analytics to integrate the genome-wide PPIs with GO data. We also introduce an interactive web application tool that visualizes a functional association network linked to a protein specified by a user. The proposed approach comprises two major components. First, the PPIs that have been generated by high-throughput methods are weighted in terms of their functional consistency using GO and its annotations. We assess two advanced semantic similarity metrics which quantify the functional association level of each interacting protein pair. We demonstrate that these measures outperform the other existing methods by evaluating their agreement to other biological features, such as sequence similarity, the presence of common Pfam domains, and core PPIs. Second, the information flow-based algorithm is employed to discover a set of proteins functionally associated with the protein in a query and their links efficiently. This algorithm reconstructs a functional association network of the query protein. The output network size can be flexibly determined by parameters.Conclusions
M-Finder provides a useful framework to investigate functional association patterns with any protein. This software will also allow users to perform further systematic analysis of a set of proteins for any specific function. It is available online at http://bionet.ecs.baylor.edu/mfinder96.
Hoi Lym Kwon Jae-Ho Kim Dong Hee Na Dae Heung Byeun Ying Wu Si Wouk Kim Eon Seon Jin Hoon Cho 《Biotechnology and Bioprocess Engineering》2013,18(5):932-941
A series of naphthoquinone-benzothiazole conjugates were synthesized as algicides, and their efficacies against harmful algal blooming species, such as Chattonella marina, Heterosigma akashiwo and Cochlodinium polykrikoides, were examined. The introduction of substituted benzothiazole at the C2 position of 1,4-naphthoquinone (compounds 1–9) resulted in higher algicidal activity against C. polykrikoides than the C6 conjugates (compounds 10–20). On the other hand, of the C6 conjugates, compounds 11 and 12 exhibited better algicidal activity against H. akashiwo, C. marina, and C. polykrikoides than the C2 conjugates. Further structure-activity analysis indicated that a replacement of the methoxy groups with hydroxyl groups (compounds 21–26) decreased the algicidal activity significantly. Among the various synthetic naphthoquinonebezothiazole conjugates tested, compound 12 was found to affect the most significant decrease in the level of C. polykrikoides growth, with an IC50 of 0.19 μM. Compound 11 was found to be the most potent inhibitor against H. akashiwo and C. polykrikoides, with IC50 values of 0.32 and 0.12 μM, respectively. Overall, these results highlight a possible method for controlling and inhibiting red tide forming algae using NQ derivatives. 相似文献
97.
Koeun Han Hee-Jin Jeong Joohee Sung Young Soo Keum Myeong-Cheoul Cho Jeong-Han Kim Jin-Kyung Kwon Byung-Dong Kim Byoung-Cheorl Kang 《Molecular breeding : new strategies in plant improvement》2013,31(3):537-548
Pungency in pepper (Capsicum annuum L.) has unique characteristics due to the alkaloid compound group, capsaicinoids, which includes capsaicin. Although capsaicinoids have been proved to have pharmacological and physiological effects on human health, the application of capsaicinoids has been limited because of their pungency. Capsinoids found in non-pungent peppers share closely related structures with capsaicinoids and show similar biological effects. Previous studies demonstrated that mutations in the p-AMT gene were related to the production of capsinoids; however, the pathway of capsinoid synthesis has not yet been fully elucidated. In this study, we performed genetic analysis to determine the mechanism of capsinoid synthesis using a F6 recombinant inbred line population. In this population, the presence/absence of capsinoids co-segregated with the genotype of the Pun1 locus, without exception. In addition, we screened the patterns of capsinoid synthesis and the correlation between the Pun1 locus and capsinoid synthesis in p-AMT mutant accessions. In Capsicum germplasms, we selected amino-acid-substituted mutants in the PLP binding domain of the p-AMT gene. Capsinoids were not synthesized with the recessive pun1 gene, regardless of the p-AMT genotype, and no relationship was found between p-AMT mutant type and capsinoid content. We concluded that the Pun1 gene, which is responsible for capsaicinoid synthesis, also controls capsinoid synthesis. 相似文献
98.
Soo-Kwon Park Do-Yeon Kwak Dong-Soo Park DongJin Shin Woon-Ha Hwang Myung-Hee Kim Yeon-Jae Hur Jun-Hyeon Cho You-Chun Song Ji-Yoon Lee Min-Hee Nam Il-Ryong Choi Jong-Hee Lee 《Molecular breeding : new strategies in plant improvement》2013,32(3):729-733
Green rice leafhopper (GRH, Nephotettix cincticeps Uhler) is one of the insect pests that damage cultivated rice in East Asia. GRH also transmits viruses such as rice dwarf virus. The mortality of GRH nymphs is high in rice cultivar Shingwang, indicating that Shingwang is resistant to GRH. Genetic analyses were performed to map GRH resistance in Shingwang using F2 and F3 populations derived from a cross between a GRH-resistant near-isogenic line (NIL-IS60) from Shingwang and recurrent parent Ilpum. Resistance to GRH in Shingwang was found to be controlled by a single dominant gene (Grh1) mapped within an approximately 670-kb region between 8.10 and 8.77 Mb on the short arm of chromosome 5. Genotypes with three simple sequence repeat markers (RM18166, RM516, and RM18171) and one indel marker (Indel 15040) co-segregated with GRH resistance controlled by the Grh1 locus. A detailed map of the Grh1 locus will facilitate marker-assisted selection of resistance to GRH in rice breeding. 相似文献
99.
100.
Bin Jiang Jeffrey Mason Anahid Jewett Jun Qian Yijiang Ding William CS Cho Xichen Zhang Yan-gao Man 《International journal of biological sciences》2013,9(1):119-133
Background: Colorectal carcinogenesis is believed to be a multi-stage process that originates with a localized adenoma, which linearly progresses to an intra-mucosal carcinoma, to an invasive lesion, and finally to metastatic cancer. This progression model is supported by tissue culture and animal model studies, but it is difficult to reconcile with several well-established observations, principally among these are that up to 25% of early stage (Stage I/II), node-negative colorectal cancer (CRC) develop distant metastasis, and that circulating CRC cells are undetectable in peripheral blood samples of up to 50% of patients with confirmed metastasis, but more than 30% of patients with no detectable metastasis exhibit such cells. The mechanism responsible for this diverse behavior is unknown, and there are no effective means to identify patients with pending, or who are at high risk for, developing metastatic CRC.Novel findings: Our previous studies of human breast and prostate cancer have shown that cancer invasion arises from the convergence of a tissue injury, the innate immune response to that injury, and the presence of tumor stem cells within tumor capsules at the site of the injury. Focal degeneration of a capsule due to age or disease attracts lymphocyte infiltration that degrades the degenerating capsules resulting in the formation of a focal disruption in the capsule, which selectively favors proliferating or “budding” of the underlying tumor stem cells. Our recent studies suggest that lymphocyte infiltration also triggers metastasis by disrupting the intercellular junctions and surface adhesion molecules within the proliferating cell buds causing their dissociation. Then, lymphocytes and tumor cells are conjoined through membrane fusion to form tumor-lymphocyte chimeras (TLCs) that allows the tumor stem cell to avail itself of the lymphocyte''s natural ability to migrate and breach cell barriers in order to intravasate and to travel to distant organs. Our most recent studies of human CRC have detected nearly identical focal capsule disruptions, lymphocyte infiltration, budding cells, and the formation of TLCs. Our studies have further shown that age- and type-matched node-positive and -negative CRC have a significantly different morphological and immunohistochemical profile and that the majority of lymphatic ducts with disseminated cells are located within the mucosa adjacent to morphologically normal appearing epithelial structures that express a stem cell-related marker.New hypothesis: Based on these findings and the growth patterns of budding cells revealed by double immunohistochemistry, we further hypothesize that metastatic spread is an early event of carcinogenesis and that budding cells overlying focal capsule disruptions represent invasion- and metastasis-initiating cells that follow one of four pathways to progress: (1) to undergo extensive in situ proliferation leading to the formation of tumor nests that subsequently invade the submucosa, (2) to migrate with associated lymphocytes functioning as “seeds” to grow in new sites, (3) to migrate and intravasate into pre-existing vascular structures by forming TLCs, or (4) to intravasate into vascular structures that are generated by the budding cells themselves. We also propose that only node-positive cases harbor stem cells with the potential for multi-lineage differentiation and unique surface markers that permit intravasation. 相似文献