全文获取类型
收费全文 | 9236篇 |
免费 | 620篇 |
国内免费 | 635篇 |
出版年
2024年 | 17篇 |
2023年 | 91篇 |
2022年 | 213篇 |
2021年 | 439篇 |
2020年 | 306篇 |
2019年 | 381篇 |
2018年 | 366篇 |
2017年 | 275篇 |
2016年 | 351篇 |
2015年 | 562篇 |
2014年 | 667篇 |
2013年 | 729篇 |
2012年 | 812篇 |
2011年 | 767篇 |
2010年 | 448篇 |
2009年 | 416篇 |
2008年 | 473篇 |
2007年 | 402篇 |
2006年 | 367篇 |
2005年 | 307篇 |
2004年 | 261篇 |
2003年 | 238篇 |
2002年 | 187篇 |
2001年 | 177篇 |
2000年 | 153篇 |
1999年 | 141篇 |
1998年 | 106篇 |
1997年 | 98篇 |
1996年 | 88篇 |
1995年 | 74篇 |
1994年 | 83篇 |
1993年 | 66篇 |
1992年 | 72篇 |
1991年 | 66篇 |
1990年 | 66篇 |
1989年 | 51篇 |
1988年 | 32篇 |
1987年 | 35篇 |
1986年 | 22篇 |
1985年 | 27篇 |
1984年 | 10篇 |
1983年 | 16篇 |
1982年 | 9篇 |
1981年 | 4篇 |
1980年 | 6篇 |
1979年 | 6篇 |
1978年 | 2篇 |
1977年 | 2篇 |
1976年 | 2篇 |
1972年 | 1篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
211.
A simple, reliable, high-throughput screening method was developed and used to assess the pharmaceutical effects of extracts of traditional Chinese herbal medicines (TCHMs). This method is based on 3-dimensional (3-D) cultures of mouse embryonic stem (mES) and human colon cancer and breast cancer cells expressing enhanced green fluorescent protein (EGFP) in polyethylene terephthalate (PET) fibrous scaffolds on modified 384-well plates with online monitoring of culture fluorescence for dynamic responses of cells to drugs present in culture media. Cell responses to deoxycholic acid and the extracts of 3 TCHMs (Ganoderma lucidum spores, Ginkgo biloba, and Epimedium brevicornum) at various concentrations were investigated for their effects on proliferation and cytotoxicity. The screening results, i.e., the growth responses of cancer cells to those drugs, were consistent with what have been reported in the literature, confirming the reliability of the new screening approach. Different from previous screening methods for both TCHMs and western medicines that used animal models or 2-D cell-based assays with single cell lines, this 3-D cell-based screening method employs both cancer and normal cells and thereby provides a way for quick, direct evaluation of the anticancer effects of TCHMs. This method also offers assessment on the side effects of TCHMs. 相似文献
212.
Haixiang Wei Gan Shen Xiaolong Deng Dong Lou Binbin Sun Hao Wu Long Long Tao Ding Jian Zhao 《Cell and tissue banking》2013,14(4):699-706
Rheumatoid arthritis (RA) is the most common degenerative arthritic cartilage and represents a disease where the prospect of stem cell therapy offers considerable hope. Currently, bone marrow (BM) represents the major source of mesenchymal stem cells (MSCs) for cell therapy. In the pathology of RA, the pro-inflammatory cytokines, such as interleukin 6 (IL-6) play a pivotal role. To investigate the direct role of IL-6 in the chondrogenic differentiation of murine MSCs (mMSCs), we isolate MSCs from the murine bone marrow, and induce MSCs chondrogenesis with different concentrations of IL-6 in vitro. Through detecting the histological and histochemical qualities of the aggregates, we demonstrate that IL-6 inhibited the differentiation of MSCs into chondrocytes in the dose-dependence manner. These findings suggest that possible strategies for improving the clinical outcome of cartilage repair procedures. 相似文献
213.
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
214.
Xiang Zhou Jennifer J. Michal Lifan Zhang Bo Ding Joan K. Lunney Bang Liu Zhihua Jiang 《International journal of biological sciences》2013,9(2):200-208
Secretion of interferons (IFNs) from virus-infected cells is a hallmark of host antiviral immunity and in fact, IFNs exert their antiviral activities through the induction of antiviral proteins. The IFN-induced protein with tetratricopeptide repeats (IFITs) family is among hundreds of IFN-stimulated genes. This family contains a cluster of duplicated loci. Most mammals have IFIT1, IFIT2, IFIT3 and IFIT5; however, bird, marsupial, frog and fish have only IFIT5. Regardless of species, IFIT5 is always adjacent to SLC16A12. IFIT family genes are predominantly induced by type I and type III interferons and are regulated by the pattern recognition and the JAK-STAT signaling pathway. IFIT family proteins are involved in many processes in response to viral infection. However, some viruses can escape the antiviral functions of the IFIT family by suppressing IFIT family genes expression or methylation of 5'' cap of viral molecules. In addition, the variants of IFIT family genes could significantly influence the outcome of hepatitis C virus (HCV) therapy. We believe that our current review provides a comprehensive picture for the community to understand the structure and function of IFIT family genes in response to pathogens in human, as well as in animals. 相似文献
215.
Ken Chen Nicholas E Navin Yong Wang Heather K Schmidt John W Wallis Beifang Niu Xian Fan Hao Zhao Michael D McLellan Katherine A Hoadley Elaine R Mardis Timothy J Ley Charles M Perou Richard K Wilson Li Ding 《Genome biology》2013,14(8):R87
Producing gene fusions through genomic structural rearrangements is a major mechanism for tumor evolution. Therefore, accurately detecting gene fusions and the originating rearrangements is of great importance for personalized cancer diagnosis and targeted therapy. We present a tool, BreakTrans, that systematically maps predicted gene fusions to structural rearrangements. Thus, BreakTrans not only validates both types of predictions, but also provides mechanistic interpretations. BreakTrans effectively validates known fusions and discovers novel events in a breast cancer cell line. Applying BreakTrans to 43 breast cancer samples in The Cancer Genome Atlas identifies 90 genomically validated gene fusions. BreakTrans is available at http://bioinformatics.mdanderson.org/main/BreakTrans 相似文献
216.
Zhaohua Ding Allen T. Newton Ran Xu Adam W. Anderson Victoria L. Morgan John C. Gore 《PloS one》2013,8(12)
Resting state functional magnetic resonance imaging (fMRI) has been commonly used to measure functional connectivity between cortical regions, while diffusion tensor imaging (DTI) can be used to characterize structural connectivity of white matter tracts. In principle combining resting state fMRI and DTI data could allow characterization of structure-function relations of distributed neural networks. However, due to differences in the biophysical origins of their signals and in the tissues to which they apply, there has been no direct integration of these techniques to date. We demonstrate that MRI signal variations and power spectra in a resting state are largely comparable between gray matter and white matter, that there are temporal correlations of fMRI signals that persist over long distances within distinct white matter structures, and that neighboring intervoxel correlations of low frequency resting state signals showed distinct anisotropy in many regions. These observations suggest that MRI signal variations from within white matter in a resting state may convey similar information as their corresponding fluctuations of MRI signals in gray matter. We thus derive a local spatio-temporal correlation tensor which captures directional variations of resting-state correlations and which reveals distinct structures in both white and gray matter. This novel concept is illustrated with in vivo experiments in a resting state, which demonstrate the potential of the technique for mapping the functional structure of neural networks and for direct integration of structure-function relations in the human brain. 相似文献
217.
OpenMP, a typical shared memory programming paradigm, has been extensively applied in high performance computing community due to the popularity of multicore architectures in recent years. The most significant feature of the OpenMP 3.0 specification is the introduction of the task constructs to express parallelism at a much finer level of detail. This feature, however, has posed new challenges for performance monitoring and analysis. In particular, task creation is separated from its execution, causing the traditional monitoring methods to be ineffective. This paper presents a mechanism to monitor task-based OpenMP programs with interposition and proposes two demonstration graphs for performance analysis as well. The results of two experiments are discussed to evaluate the overhead of monitoring mechanism and to verify the effects of demonstration graphs using the BOTS benchmarks. 相似文献
218.
Zhanfeng Liu Yongbiao Lin Hongfang Lu Mingmao Ding Yaowen Tan Shejin Xu Shenglei Fu 《PloS one》2013,8(10)
Orchard understory represents an important component of the orchards, performing numerous functions related to soil quality, water relations and microclimate, but little attention has been paid on its effect on soil C sequestration. In the face of global climate change, fruit producers also require techniques that increase carbon (C) sequestration in a cost-effective manner. Here we present a case study to compare the effects of understory management (sod culture vs. clean tillage) on soil C sequestration in four subtropical orchards. The results of a 10-year study indicated that the maintenance of sod significantly enhanced the soil C stock in the top 1 m of orchard soils. Relative to clean tillage, sod culture increased annual soil C sequestration by 2.85 t C ha-1, suggesting that understory management based on sod culture offers promising potential for soil carbon sequestration. Considering that China has the largest area of orchards in the world and that few of these orchards currently have sod understories, the establishment and maintenance of sod in orchards can help China increase C sequestration and greatly contribute to achieving CO2 reduction targets at a regional scale and potentially at a national scale. 相似文献
219.
Jiayi Tong Jiandong Ding Xiangbo Shen Long Chen Yeping Bian Genshan Ma Yuyu Yao Fang Yang 《PloS one》2013,8(11)
Objective
This study evaluated the effects of ultrasound combined with the homemade nitric oxide (NO) micro-bubble destruction on the in vitro proliferation, apoptosis, and migration of mesenchymal stem cells (MSCs). Furthermore, we studied whether or not irradiation of the NO micro-bubble combined with bone-marrow derived MSC infusion had a better effect on treating myocardial infarction. The possible mechanism of MSC delivery into the infarcted myocardium was also investigated.Methods
The murine bone marrow-derived MSCs were isolated, cultured, irradiated, and combined with different concentrations of NO microbubbles. MTT proliferation assay, annexin V-FITC apoptosis detection, migration assay, and RT-PCR were performed 24 h after the irradiation. The NO micro-bubbles was a intravenously injected, followed by the infusion of MSCs, which were labeled by CM-Dil. Myocardium was harvested 48 h later and the distribution of MSCs was observed by laser scanning confocal microscope after frozen sectioning. Echocardiography, histological examination, RT-PCR, and western blotting were performed four weeks after the cell transplantation.Results
Ultrasound combined with 1:70 NO micro-bubbles had no significant impact on the proliferation or apoptosis of MSCs. Transwell chamber findings demonstrated that MSCs migrated more efficiently in group that underwent ultrasound combined with 1:70 NO micro-bubbles. The Real-time PCR results indicated that the expression of CXCR4 was much higher in the group undergoing ultrasound combined with 1:70 NO micro-bubbles. The normalized fluorescence intensity greatly increased in the group of US+NO micro-bubbles and the cardiac function was also markedly improved. Immunohistochemical staining showed that the capillary density was much greater in the group of US+NO micro-bubbles as compared to that of the other groups. RT-PCR and western blotting also revealed a higher SDF-1 and VEGF expression in the group of US+NO micro-bubbles.Conclusions
NO micro-bubbles could be used in the cell transplantation, which efficiently promoted the MSC homing into the infarcted myocardium. 相似文献220.
Shenjie Tang Shouyong Tan Lan Yao Fujian Li Li Li Xinzhi Guo Yidian Liu Xiaohui Hao Yanqiong Li Xiuxiu Ding Zhanjun Zhang Li Tong Jianan Huang 《PloS one》2013,8(12)