全文获取类型
收费全文 | 28056篇 |
免费 | 2019篇 |
国内免费 | 1001篇 |
专业分类
电工技术 | 1640篇 |
综合类 | 912篇 |
化学工业 | 6926篇 |
金属工艺 | 967篇 |
机械仪表 | 1176篇 |
建筑科学 | 351篇 |
矿业工程 | 216篇 |
能源动力 | 7985篇 |
轻工业 | 2745篇 |
水利工程 | 53篇 |
石油天然气 | 118篇 |
武器工业 | 52篇 |
无线电 | 2873篇 |
一般工业技术 | 2885篇 |
冶金工业 | 712篇 |
原子能技术 | 329篇 |
自动化技术 | 1136篇 |
出版年
2024年 | 77篇 |
2023年 | 625篇 |
2022年 | 1690篇 |
2021年 | 1959篇 |
2020年 | 1158篇 |
2019年 | 1096篇 |
2018年 | 863篇 |
2017年 | 1055篇 |
2016年 | 938篇 |
2015年 | 884篇 |
2014年 | 1548篇 |
2013年 | 1709篇 |
2012年 | 1713篇 |
2011年 | 2514篇 |
2010年 | 1839篇 |
2009年 | 1571篇 |
2008年 | 1604篇 |
2007年 | 1494篇 |
2006年 | 1229篇 |
2005年 | 992篇 |
2004年 | 786篇 |
2003年 | 598篇 |
2002年 | 573篇 |
2001年 | 452篇 |
2000年 | 364篇 |
1999年 | 288篇 |
1998年 | 263篇 |
1997年 | 209篇 |
1996年 | 171篇 |
1995年 | 150篇 |
1994年 | 126篇 |
1993年 | 105篇 |
1992年 | 82篇 |
1991年 | 60篇 |
1990年 | 49篇 |
1989年 | 47篇 |
1988年 | 36篇 |
1987年 | 22篇 |
1986年 | 23篇 |
1985年 | 28篇 |
1984年 | 16篇 |
1983年 | 12篇 |
1982年 | 13篇 |
1981年 | 9篇 |
1980年 | 14篇 |
1979年 | 7篇 |
1978年 | 3篇 |
1976年 | 2篇 |
1975年 | 2篇 |
1951年 | 5篇 |
排序方式: 共有10000条查询结果,搜索用时 11 毫秒
91.
Hiroko Ishii Maram H. Zahra Atushi Takayanagi Masaharu Seno 《International journal of molecular sciences》2021,22(4)
Cripto-1 is a member of the EGF-CFC/FRL1/Cryptic family and is involved in embryonic development and carcinogenesis. We designed a novel anti-Cripto-1 artificial antibody and assessed the recognition to the antigen and the potential to suppress the growth of cancer stem cells. First, single chain antibody clones were isolated by bio-panning with the affinity to recombinant Cripto-1 protein from our original phage-display library. Then, the variable regions of heavy chain VH and light chain VL in each clone were fused to constant regions of heavy chain CH and light chain CL regions respectively. These fused genes were expressed in ExpiCHO-S cells to produce artificial humanized antibodies against Cripto-1. After evaluation of the expression levels, one clone was selected and the anti-Cripto-1 antibody was produced and purified. The purified antibody showed affinity to recombinant Cripto-1 at 1.1 pmol and immunoreactivity to cancer tissues and cell lines. The antibody was available to detect the immunoreactivity in tissue microarrays of malignant tumors as well as in Cripto-1 overexpressing cells. Simultaneously, the antibody exhibited the potential to suppress the growth of human colon cancer derived GEO cells overexpressing Cripto-1 with IC50 at approximately 110 nM. The artificially humanized antibody is proposed to be a good candidate to target cancer cells overexpressing Cripto-1. 相似文献
92.
Barbora Peltanova Marketa Liskova Jaromir Gumulec Martina Raudenska Hana Holcova Polanska Tomas Vaculovic David Kalfert Marek Grega Jan Plzak Jan Betka Michal Masarik 《International journal of molecular sciences》2021,22(4)
Cancer-associated fibroblasts (CAFs) are one of the most abundant and critical components of the tumor stroma. CAFs can impact many important steps of cancerogenesis and may also influence treatment resistance. Some of these effects need the direct contact of CAFs and cancer cells, while some involve paracrine signals. In this study, we investigated the ability of head and neck squamous cell carcinomas (HNSCC) patient-derived CAFs to promote or inhibit the colony-forming ability of HNSCC cells. The effect of cisplatin on this promoting or inhibiting influence was also studied. The subsequent analysis focused on changes in the expression of genes associated with cancer progression. We found that cisplatin response in model HNSCC cancer cells was modified by coculture with CAFs, was CAF-specific, and different patient-derived CAFs had a different “sensitizing ratio”. Increased expression of VEGFA, PGE2S, COX2, EGFR, and NANOG in cancer cells was characteristic for the increase of resistance. On the other hand, CCL2 expression was associated with sensitizing effect. Significantly higher amounts of cisplatin were found in CAFs derived from patients who subsequently experienced a recurrence. In conclusion, our results showed that CAFs could promote and/or inhibit colony-forming capability and cisplatin resistance in HNSCC cells via paracrine effects and subsequent changes in gene expression of cancer-associated genes in cancer cells. 相似文献
93.
Su-Min Baek Seoung-Woo Lee Tae-Un Kim Seong-Kyoon Choi Sungho Yun Won-Jae Lee Se-Hyeon Han Il-Hwa Hong Sang-Joon Park Tae-Hwan Kim Kyu-Shik Jeong Jin-Kyu Park 《International journal of molecular sciences》2021,22(5)
Senescence marker protein 30 (SMP30) is a cell survival factor playing an important role in vitamin C synthesis and antiapoptosis. Moreover, its cytoprotective role suggests a possibility to be related to cancer cell survival. Mammary carcinoma is a common cancer in both humans and animals. Because of its histopathological diversity, especially in the early stage, histopathological diagnosis may be complicated; therefore, a diagnostic marker is helpful for confirmation. The present study analyzed the expression pattern of SMP30 in mammary carcinoma in humans, dogs, and cats. Immunohistochemistry, immunofluorescence, and western blot analysis were used to investigate SMP30 expression patterns. The expression was specifically observed in neoplastic glandular epithelial cells. The expression increased with the malignancy of glandular epithelial cells with a highly proliferative status. However, SMP30 expression was low in normal mammary gland tissues or well-differentiated adenoma tissues. The patterns were consistently reproduced in canine primary mammary carcinoma cells and MCF-7 and MDA-MB-231 human carcinoma cell lines. This study provides useful information to understand SMP30 expression in various stages of mammary carcinoma and to suggest its utility as a pan-species diagnostic marker, thereby helping to establish strategies for diagnosing mammary carcinoma in several species. 相似文献
94.
Emilia Piosik Marta Ziegler-Borowska Dorota Cheminiak-Dudkiewicz Tomasz Martyski 《International journal of molecular sciences》2021,22(5)
An adsorption process of magnetite nanoparticles functionalized with aminated chitosan (Fe3O4-AChit) showing application potential in nanomedicine into cell membrane models was studied. The cell membrane models were formed using a Langmuir technique from three selected phospholipids with different polar head-groups as well as length and carbon saturation of alkyl chains. The research presented in this work reveals the existence of membrane model composition-dependent regulation of phospholipid-nanoparticle interactions. The influence of the positively charged Fe3O4-AChit nanoparticles on a Langmuir film stability, phase state, and textures is much greater in the case of these formed by negatively charged 1,2-dipalmitoyl-sn-glycero-3-phospho-rac-(1-glycerol) (DPPG) than those created by zwitterionic 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) and 2-oleoyl-1-palmitoyl-sn-glycero-3-phosphocholine (POPC). The adsorption kinetics recorded during penetration experiments show that this effect is caused by the strongest adsorption of the investigated nanoparticles into the DPPG monolayer driven very likely by the electrostatic attraction. The differences in the adsorption strength of the Fe3O4-AChit nanoparticles into the Langmuir films formed by the phosphatidylcholines were also observed. The nanoparticles adsorbed more easily into more loosely packed POPC monolayer. 相似文献
95.
Monika Bednarczyk Carolina Medina-Montano Frederic Julien Fittler Henner Stege Meike Roskamp Michael Kuske Christian Langer Marco Vahldieck Evelyn Montermann Ingrid Tubbe Nadine Rhrig Andrzej Dzionek Stephan Grabbe Matthias Bros 《International journal of molecular sciences》2021,22(6)
The development of nanocarriers (NC) for biomedical applications has gained large interest due to their potential to co-deliver drugs in a cell-type-targeting manner. However, depending on their surface characteristics, NC accumulate serum factors, termed protein corona, which may affect their cellular binding. We have previously shown that NC coated with carbohydrates to enable biocompatibility triggered the lectin-dependent complement pathway, resulting in enhanced binding to B cells via complement receptor (CR)1/2. Here we show that such NC also engaged all types of splenic leukocytes known to express CR3 at a high rate when NC were pre-incubated with native mouse serum resulting in complement opsonization. By focusing on dendritic cells (DC) as an important antigen-presenting cell type, we show that CR3 was essential for binding/uptake of complement-opsonized NC, whereas CR4, which in mouse is specifically expressed by DC, played no role. Further, a minor B cell subpopulation (B-1), which is important for first-line pathogen responses, and co-expressed CR1/2 and CR3, in general, engaged NC to a much higher extent than normal B cells. Here, we identified CR-1/2 as necessary for binding of complement-opsonized NC, whereas CR3 was dispensable. Interestingly, the binding of complement-opsonized NC to both DC and B-1 cells affected the expression of activation markers. Our findings may have important implications for the design of nano-vaccines against infectious diseases, which codeliver pathogen-specific protein antigen and adjuvant, aimed to induce a broad adaptive cellular and humoral immune response by inducing cytotoxic T lymphocytes that kill infected cells and pathogen-neutralizing antibodies, respectively. Decoration of nano-vaccines either with carbohydrates to trigger complement activation in vivo or with active complement may result in concomitant targeting of DC and B cells and thereby may strongly enhance the extent of dual cellular/humoral immune responses. 相似文献
96.
97.
98.
Nadine Kretschmer Antje Hufner Christin Durchschein Katrin Popodi Beate Rinner Birgit Lohberger Rudolf Bauer 《International journal of molecular sciences》2021,22(5)
Melanoma is the deadliest form of skin cancer and accounts for about three quarters of all skin cancer deaths. Especially at an advanced stage, its treatment is challenging, and survival rates are very low. In previous studies, we showed that the constituents of the roots of Onosma paniculata as well as a synthetic derivative of the most active constituent showed promising results in metastatic melanoma cell lines. In the current study, we address the question whether we can generate further derivatives with optimized activity by synthesis. Therefore, we prepared 31, mainly novel shikonin derivatives and screened them in different melanoma cell lines (WM9, WM164, and MUG-Mel2 cells) using the XTT viability assay. We identified (R)-1-(1,4-dihydro-5,8-dihydroxy-1,4-dioxonaphthalen-2-yl)-4-methylpent-3-enyl 2-cyclopropyl-2-oxoacetate as a novel derivative with even higher activity. Furthermore, pharmacological investigations including the ApoToxGloTM Triplex assay, LDH assay, and cell cycle measurements revealed that this compound induced apoptosis and reduced cells in the G1 phase accompanied by an increase of cells in the G2/M phase. Moreover, it showed hardly any effects on the cell membrane integrity. However, it also exhibited cytotoxicity against non-tumorigenic cells. Nevertheless, in summary, we could show that shikonin derivatives might be promising drug leads in the treatment of melanoma. 相似文献
99.
Natalia Ziemkiewicz Genevieve Hilliard Nicholas A. Pullen Koyal Garg 《International journal of molecular sciences》2021,22(6)
Skeletal muscle regeneration is highly dependent on the inflammatory response. A wide variety of innate and adaptive immune cells orchestrate the complex process of muscle repair. This review provides information about the various types of immune cells and biomolecules that have been shown to mediate muscle regeneration following injury and degenerative diseases. Recently developed cell and drug-based immunomodulatory strategies are highlighted. An improved understanding of the immune response to injured and diseased skeletal muscle will be essential for the development of therapeutic strategies. 相似文献