全文获取类型
收费全文 | 5398篇 |
免费 | 410篇 |
国内免费 | 301篇 |
专业分类
6109篇 |
出版年
2024年 | 8篇 |
2023年 | 74篇 |
2022年 | 126篇 |
2021年 | 235篇 |
2020年 | 181篇 |
2019年 | 228篇 |
2018年 | 201篇 |
2017年 | 177篇 |
2016年 | 284篇 |
2015年 | 323篇 |
2014年 | 369篇 |
2013年 | 430篇 |
2012年 | 493篇 |
2011年 | 438篇 |
2010年 | 267篇 |
2009年 | 215篇 |
2008年 | 305篇 |
2007年 | 244篇 |
2006年 | 207篇 |
2005年 | 179篇 |
2004年 | 187篇 |
2003年 | 141篇 |
2002年 | 145篇 |
2001年 | 83篇 |
2000年 | 54篇 |
1999年 | 74篇 |
1998年 | 48篇 |
1997年 | 54篇 |
1996年 | 38篇 |
1995年 | 30篇 |
1994年 | 32篇 |
1993年 | 21篇 |
1992年 | 36篇 |
1991年 | 13篇 |
1990年 | 13篇 |
1989年 | 18篇 |
1988年 | 15篇 |
1987年 | 13篇 |
1986年 | 11篇 |
1985年 | 13篇 |
1984年 | 12篇 |
1983年 | 19篇 |
1982年 | 5篇 |
1980年 | 5篇 |
1979年 | 6篇 |
1978年 | 5篇 |
1977年 | 5篇 |
1975年 | 6篇 |
1974年 | 5篇 |
1973年 | 6篇 |
排序方式: 共有6109条查询结果,搜索用时 15 毫秒
101.
102.
Qingyu Lang Haoxing Zhang Jie Li Fang Xie Yifeng Zhang Bo Wan Long Yu 《Molecular biology reports》2010,37(3):1577-1583
The Aurora kinases play a critical role in mitosis and have been suggested as promising targets for cancer therapy due to
their frequent overexpression in a variety of tumors. Compared with established inhibitors of cell division such as the anti-tubulins,
novel agents target mitotic enzymes and show similar efficacy but with fewer side effects. Several small-molecule inhibitors
of Aurora kinases have been developed as anticancer agents, some of which have progressed to early clinical evaluation. Here
we identified 3-hydroxyflavone as a novel Aurora B inhibitor through high throughput screening. 3-Hydroxyflavone showed potent
inhibition to Aurora B with the IC50 on a nanomolar basis in the enzyme-based kinase activity assay. In the cell-based western blotting analysis, 3-hydroxyflavone
dramatically decreased the phosphorylation level of Histone H3 on the site of serine 10, demonstrating the potent endogenous
Aurora B activity inhibition in cell level. The followed cell image analysis provided the consist result. To make it clear
whether 3-hydroxyflavone inhibited Aurora B by direct binding or not, SPR analysis was carried out to measure the affinity
of interaction between Aurora B protein and 3-hydroxyflavone and the result proved the binding with high affinity. Usually
Aurora activity suppression induced cancer cell proliferation inhibition. Colony formation and cell viability with/without
treatment of 3-hydroxyflavone were measured using CCK-8. The growth suppression under 3-hydroxyflavone present and the growth
recovery after being released gave strong evidence that presence of 3-hydroxyflavone efficiently inhibited the fast growth
of cancer cells. 相似文献
103.
104.
105.
控失尿素对稻田氨挥发、氮素转运及利用效率的影响 总被引:7,自引:0,他引:7
通过田间试验,以普通尿素分次施用处理(CU)为对照,研究了控失尿素分次施用(LCUS)和一次施用(LCUB)对水稻田土壤氨挥发特征、水稻氮素营养状况、稻谷产量及氮肥利用效率的影响. 结果表明: 普通尿素分次施用、控失尿素分次施用和控失尿素一次施用条件下,生育期氨挥发总量占总施氮量的比例分别为15.8%、13.4%和19.7%. 与普通尿素分次施用处理相比,控失尿素分次施用处理可降低土壤氨挥发损失量4.4 kg N·hm-2,降幅达18.0%,而控失尿素一次施用处理稻田土壤氨挥发总量却增加了7.2 kg N·hm-2,增幅达24.7%. 与普通尿素分次施用处理相比,控失尿素分次施用处理的水稻叶片叶绿素、籽粒和茎叶氮含量与氮素积累量、稻谷产量均有不同程度提高,氮肥利用率显著提高了7.6%,但氮素转运量、转运率和对穗氮贡献率均显著降低,而控失尿素一次施用处理的水稻叶片叶绿素、籽粒和茎叶氮含量与氮素积累量以及氮肥利用率均显著降低,氮素转运量、转运率、对穗氮贡献率以及稻谷产量无显著差异. 综上所述,控失尿素分次施用处理可以在保证稻谷稳产的同时,有效降低稻田土壤氨挥发损失,改善植株氮素营养状况,显著提高氮肥利用效率. 相似文献
106.
In vivo inhibition of megakaryocyte and platelet production by platelet factor 4 in mice. 总被引:1,自引:0,他引:1
Z C Han S Bellucci E Bodevin H Y Wan Z X Shen J P Caen 《Comptes rendus de l'Académie des sciences. Série III, Sciences de la vie》1991,313(12):553-558
The in vivo effect of human platelet factor 4 (PF4) on murine megakaryocytopoiesis and thrombopoiesis was studied. Administration of PF4 induced a dose-dependent decrease in the numbers of megakaryocytes and their progenitor cells (CFU-MK), continuing for 1 week after the injection. However, the size of megakaryocytes and their colonies was not changed following PF4 injection. Platelet levels were significantly decreased at days 3-4. The number of CFU-GM was decreased at days 1-2. White blood cells and hemoglobin were unaffected by PF4. These data indicate that PF4 inhibits megakaryocyte and platelet production in vivo by acting on the early stage of megakaryocyte development. 相似文献
107.
Lung cancer is one of the leading malignancies worldwide, but the regulatory mechanism of its growth and metastasis is still poorly understood. We investigated the possible expression of immunoglobulin G (IgG) genes in squamous cell carcinomas and adenocarcinomas of the lung and related cancer cell lines. Abundant mRNA of IgG and essential enzymes for IgG synthesis, recombination activation genes 1, 2 (RAG1, 2) and activation-induced cytidine deaminase (AID) were detected in the cancer cells but not in adjacent normal lung tissue or normal lung epithelial cell line. The extents of IgG expression in 86 lung cancers were found to associate with clinical stage, pathological grade and lymph node metastasis. We found that knockdown of IgG with siRNA resulted in decreases of cellular proliferation, migration and attachment for cultured lung cancer cells. Metastasis-associated gene 1 (MTA1) appeared to be co-expressed with IgG in lung cancer cells. Statistical analysis showed that the rate of IgG expression was significantly correlated to that of MTA1 and to lymph node metastases. Inhibition of MTA1 gene expression with siRNA also led to decreases of cellular migration and attachment for cultured lung cancer cells. These evidences suggested that inhibition of cancer migration and attachment induced by IgG down-regulation might be achieved through MTA1 regulatory pathway. Our findings suggest that lung cancer-produced IgG is likely to play an important role in cancer growth and metastasis with significant clinical implications. 相似文献
108.
Hui Yang Lu Luo Yuying Li Huadong Li Xiurong Zhang Kun Zhang Suqing Zhu Xuanlin Li Yingjie Li Yongshan Wan Fengzhen Liu 《Plant biotechnology journal》2023,21(9):1785-1798
Cultivated peanut (Arachis hypogaea L.) is an important oil and cash crop. Pod size is one of the major traits determining yield and commodity characteristic of peanut. Fine mapping of quantitative trait locus (QTL) and identification of candidate genes associated with pod size are essential for genetic improvement and molecular breeding of peanut varieties. In this study, a major QTL related to pod size, qAHPS07, was fine mapped to a 36.46 kb interval on chromosome A07 using F2, recombinant inbred line (RIL) and secondary F2 populations. qAHPS07 explained 38.6%, 23.35%, 37.48%, 25.94% of the phenotypic variation for single pod weight (SPW), pod length (PL), pod width (PW) and pod shell thickness (PST), respectively. Whole genome resequencing and gene expression analysis revealed that a RuvB-like 2 protein coding gene AhRUVBL2 was the most likely candidate for qAHPS07. Overexpression of AhRUVBL2 in Arabidopsis led to larger seeds and plants than the wild type. AhRUVBL2-silenced peanut seedlings represented small leaves and shorter main stems. Three haplotypes were identified according to three SNPs in the promoter of AhRUVBL2 among 119 peanut accessions. Among them, SPW, PW and PST of accessions carrying Hap_ATT represent 17.6%, 11.2% and 26.3% higher than those carrying Hap_GAC,respectively. In addition, a functional marker of AhRUVBL2 was developed. Taken together, our study identified a key functional gene of peanut pod size, which provides new insights into peanut pod size regulation mechanism and offers practicable markers for the genetic improvement of pod size-related traits in peanut breeding. 相似文献
109.
Anti-cancer activities of tea epigallocatechin-3-gallate in breast cancer patients under radiotherapy 总被引:4,自引:0,他引:4
Zhang G Wang Y Zhang Y Wan X Li J Liu K Wang F Liu K Liu Q Yang C Yu P Huang Y Wang S Jiang P Qu Z Luan J Duan H Zhang L Hou A Jin S Hsieh TC Wu E 《Current molecular medicine》2012,12(2):163-176
The purpose of this study was to test the hypothesis that administration of epigallocatechin-3-gallate (EGCG), a polyphenol present in abundance in widely consumed tea, inhibits cell proliferation, invasion, and angiogenesis in breast cancer patients. EGCG in 400 mg capsules was orally administered three times daily to breast cancer patients undergoing treatment with radiotherapy. Parameters related to cell proliferation, invasion, and angiogenesis were analyzed while blood samples were collected at different time points to determine efficacy of the EGCG treatment. Compared to patients who received radiotherapy alone, those given radiotherapy plus EGCG for an extended time period (two to eight weeks) showed significantly lower serum levels of vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), and reduced activation of metalloproteinase-9 and metalloproteinase-2 (MMP9/MMP2). Addition of sera obtained from patients treated with combination of radiotherapy and EGCG feeding for 2-8 weeks to in vitro cultures of highly-metastatic human MDA-MB-231 breast cancer cells resulted in the following significant changes: (1) suppression of cell proliferation and invasion; (2) arrest of cell cycles at the G0/G1 phase; (3) reduction of activation of MMP9/MMP2, expressions of Bcl-2/Bax, c-Met receptor, NF-κB, and the phosphorylation of Akt. MDA-MB-231 cells exposed to 5-10 μM EGCG also showed significant augmentation of the apoptosis inducing effects of γ-radiation, concomitant with reduced NF-κB protein level and AKT phosphorylation. These results provide hitherto unreported evidence that EGCG potentiated efficacy of radiotherapy in breast cancer patients, and raise the possibility that this tea polyphenol has potential to be a therapeutic adjuvant against human metastatic breast cancer. 相似文献
110.
During epithelial morphogenesis, cells not only maintain tight adhesion for epithelial integrity but also allow dynamic intercellular movement to take place within cell sheets. How these seemingly opposing processes are coordinated is not well understood. Here, we report that the actin disassembly factors AIP1 and cofilin are required for remodeling of adherens junctions (AJs) during ommatidial precluster formation in Drosophila eye epithelium, a highly stereotyped cell rearrangement process which we describe in detail in our live imaging study. AIP1 is enriched together with F-actin in the apical region of preclusters, whereas cofilin displays a diffuse and uniform localization pattern. Cofilin overexpression completely rescues AJ remodeling defects caused by AIP1 loss of function, and cofilin physically interacts with AIP1. Pharmacological reduction of actin turnover results in similar AJ remodeling defects and decreased turnover of E-cadherin, which also results from AIP1 deficiency, whereas an F-actin-destabilizing drug affects AJ maintenance and epithelial integrity. Together with other data on actin polymerization, our results suggest that AIP1 enhances cofilin-mediated actin disassembly in the apical region of precluster cells to promote remodeling of AJs and thus intercellular movement, but also that robust actin polymerization promotes AJ general adhesion and integrity during the remodeling process. 相似文献