全文获取类型
收费全文 | 2778篇 |
免费 | 178篇 |
国内免费 | 1篇 |
专业分类
2957篇 |
出版年
2023年 | 14篇 |
2022年 | 35篇 |
2021年 | 85篇 |
2020年 | 45篇 |
2019年 | 61篇 |
2018年 | 60篇 |
2017年 | 48篇 |
2016年 | 89篇 |
2015年 | 109篇 |
2014年 | 163篇 |
2013年 | 202篇 |
2012年 | 214篇 |
2011年 | 212篇 |
2010年 | 186篇 |
2009年 | 121篇 |
2008年 | 117篇 |
2007年 | 138篇 |
2006年 | 125篇 |
2005年 | 125篇 |
2004年 | 78篇 |
2003年 | 94篇 |
2002年 | 87篇 |
2001年 | 43篇 |
2000年 | 51篇 |
1999年 | 34篇 |
1998年 | 23篇 |
1997年 | 15篇 |
1996年 | 11篇 |
1995年 | 18篇 |
1993年 | 13篇 |
1992年 | 24篇 |
1991年 | 11篇 |
1990年 | 12篇 |
1989年 | 19篇 |
1988年 | 17篇 |
1987年 | 9篇 |
1986年 | 21篇 |
1985年 | 25篇 |
1984年 | 12篇 |
1982年 | 13篇 |
1981年 | 10篇 |
1980年 | 12篇 |
1979年 | 13篇 |
1978年 | 18篇 |
1976年 | 10篇 |
1975年 | 9篇 |
1973年 | 13篇 |
1972年 | 9篇 |
1971年 | 10篇 |
1969年 | 8篇 |
排序方式: 共有2957条查询结果,搜索用时 15 毫秒
101.
Hongyun Gan Yaqing Zhang Qingyun Zhou Lierui Zheng Xiaofeng Xie Vishnu Priya Veeraraghavan Surapaneni Krishna Mohan 《Journal of biochemical and molecular toxicology》2019,33(10)
Breast cancer is a prevalent of tumoregenesis in women and reports for the maximum mortality and morbidity in the global. Ginger (Zingiber officinale) is the mainly widespread spice and herbal remedies used in the world. Since antique periods, ginger has been used in Greece, India and China for the curing of upset stomach, nausea, diarrhea, colds, and headaches. The current work was planned to explore the anticancer properties of zingerone (ZO) toward 7,12‐dimethylbenz(a)anthracene (DMBA)‐treated mammary carcinogenesis in Sprague‐Dawley (SD) rats and MCF‐7 mammary cancer cells. The mammary carcinogenesis was produced through a single dosage of DMBA (20 mg/kg bwt) mixed in soya oil (1 mL) administrated intragastrically with a gavage. We found improved concentrations of lipid peroxidation (LOOH and TBARS), carcinoembryonic antigen, lowered levels of enzymatic (CAT, GPx, and SOD), and nonenzymatic (vitamin E, GSH, and vitamin C) antioxidant in mammary tissues and plasma of DMBA‐induced cancer bearing animals. Moreover, augmented concentrations of phase I (Cyt‐b5 and CYP450) and reduced levels of phase II (GR and GST) detoxification microsomal proteins in mammary tissues were noticed. ZO administrations significantly reverted back to all these parameters in this way, showing efficient of anticancer effect. Furthermore, our in vitro study also supported the anticancer effect of the treatment of ZO were noticed loss of cell viability, improved reactive oxygen species formation, and reduced MMP. Furthermore, the status of apoptosis proteins such as Bcl‐2, Bax, and Bid expressions was determined by using Western blot analysis techniques. Overall, these results proposed the anticancer effect of ZO toward DMBA‐induced mammary cancer in SD animals and Michigan cancer foundation‐7 mammary cancer cells. 相似文献
102.
Ping Su Vishnu Priya Veeraraghavan Surapaneni Krishna Mohan Wang Lu 《Journal of biochemical and molecular toxicology》2019,33(12)
Zingerone (ZO), an active phenolic agent derived from Zingiber officinale (Ginger), has many pharmacological properties such as antioxidant, antiangiogenic, and antitumor. However, its potential value in cancer and the mechanism by which ZO wields its therapeutic effects remain obscure. Therefore, in this current study, we explored the effects of ZO on suppressing cell proliferation and enhancing apoptosis in colon cancer cells (HCT116). Our results indicated that ZO significantly enhances the production of reactive oxygen species, lipid peroxidation (thiobarbituric acid reactive substance [TBARS]), and loss of cell viability; and reduces mitochondrial membrane potential and antioxidant levels (SOD, CAT, and GSH) in ZO‐treated HCT116 cells in a dose‐dependent (2.5, 5, and 10 µM) manner. Furthermore, ZO induces oxidative stress‐mediated apoptosis as evidenced by apoptotic morphological changes predicted by AO/EtBr, Hoechst staining and further confirmed by comet assay. Moreover, immunoblotting techniques showed that ZO treatment effectively enhances Bax, caspase‐9, and caspase‐3 expressions and decreases the expression of Bcl‐2 in colon cancer cells. Together, our results evidenced that the antitumor effects of ZO reduce cell proliferation and stimulate apoptosis through modulating pro‐ and antiapoptotic molecular events in HCT116 colon cancer cells. Therefore, based on our findings, ZO may be used as a therapeutic agent for the treatment of colon cancer. 相似文献
103.
Jun-Jiao Li Lei Zhou Chun-Mei Yin Dan-Dan Zhang Steven J. Klosterman Bao-Li Wang Jian Song Dan Wang Xiao-Ping Hu Krishna V. Subbarao Jie-Yin Chen Xiao-Feng Dai 《Environmental microbiology》2019,21(12):4852-4874
Verticillium dahliae is a soil-borne fungus that causes vascular wilt on numerous plants worldwide. The fungus survives in the soil for up to 14 years by producing melanized microsclerotia. The protective function of melanin in abiotic stresses is well documented. Here, we found that the V. dahliae tetraspan transmembrane protein VdSho1, a homolog of the Saccharomyces cerevisiae Sho1, acts as an osmosensor, and is required for plant penetration and melanin biosynthesis. The deletion mutant ΔSho1 was incubated on a cellophane membrane substrate that mimics the plant epidermis, revealing that the penetration of ΔSho1 strain was reduced compared to the wild-type strain. Furthermore, VdSho1 regulates melanin biosynthesis by a signalling mechanism requiring a kinase-kinase signalling module of Vst50-Vst11-Vst7. Strains, ΔVst50, ΔVst7 and ΔVst11 also displayed defective penetration and melanin production like the ΔSho1 strain. Defects in penetration and melanin production in ΔSho1 were restored by overexpression of Vst50, suggesting that Vst50 lies downstream of VdSho1 in the regulatory pathway governing penetration and melanin biosynthesis. Data analyses revealed that the transmembrane portion of VdSho1 was essential for both membrane penetration and melanin production. This study demonstrates that Vst50-Vst11-Vst7 module regulates VdSho1-mediated plant penetration and melanin production in V. dahliae, contributing to virulence. 相似文献
104.
105.
Anuradha Arnab Banerjee Amitabh Krishna 《Molecular reproduction and development》2019,86(12):1963-1980
The aim of this study was to evaluate the effect of putrescine on ovarian activity and the rate of embryonic development in Cynopterus sphinx during delayed development. The result showed the presence of a rate‐limiting enzyme, ornithine decarboxylase‐1, in both ovary and utero‐embryonic unit of C. sphinx suggests a synthesis of putrescine in these sites. The corpus luteum showed increased, whereas utero‐embryonic unit showed decreased production of putrescine during delayed development as compared with the normal development. The bat treated in vivo with putrescine during delayed development showed increase in progesterone and estradiol synthesis, correlated with increased expression of luteinizing hormone receptor, steroidogenic acute receptor protein, and 3β‐hydroxysteroid dehydrogenase through extracellular signal‐regulated kinase (ERK1/2)‐mediated pathway in the ovary; but showed increase in the weight and expression of progesterone receptor (PR), B‐cell lymphoma 2, proliferating cell nucleus antigen, and vascular endothelial growth factor proteins in utero‐embryonic unit. The in vitro treatment of putrescine showed stimulatory whereas treatment with an inhibitor of putrescine, 2‐difluoromethylornithine caused an inhibitory effect on ovarian progesterone synthesis and cell proliferation, and cell survival in the utero‐embryonic unit. In conclusion, the putrescine showed two separate roles during embryonic diapause, high concentration of putrescine in the ovary may support corpus luteum and basal synthesis of progesterone, whereas a low level of putrescine causes retarded embryonic development by inhibiting cell proliferation in the utero‐embryonic unit. The bat treated with putrescine either directly promotes cell proliferation, cell survival, and angiogenic activities or acts indirectly increasing PR on utero‐embryonic unit thereby activating development in delayed embryo in C. sphinx. 相似文献
106.
Suppressors of zyg-1 define regulators of centrosome duplication and nuclear association in Caenorhabditis elegans 下载免费PDF全文
In Caenorhabditis elegans, the kinase ZYG-1 is required for centrosome duplication. To identify factors that interact with ZYG-1, we used a classical genetic approach and identified 21 szy (suppressor of zyg-1) genes that when mutated restore partial viability to a zyg-1 mutant. None of the suppressors render animals completely independent of zyg-1 activity and analysis of a subset of the suppressors indicates that all restore the normal process of centrosome duplication to zyg-1 mutants. Thirteen of these suppressor mutations confer phenotypes of their own and cytological examination reveals that these genes function in a variety of cellular processes including cell cycle timing, microtubule organization, cytokinesis, chromosome segregation, and centrosome morphology. Interestingly, several of the szy genes play a role in attaching the centrosome to the nuclear envelope. We have found that one such szy gene is sun-1, a gene encoding a nuclear envelope component. We further show that the role of SUN-1 in centrosome duplication is distinct from its role in attachment. Our approach has thus identified numerous candidate regulators of centrosome duplication and uncovered an unanticipated regulatory mechanism involving factors that tether the centrosome to the nucleus. 相似文献
107.
We previously showed that bone marrow stem cells participate in the tumor vessel expansion that supports the growth of Ewing's sarcoma tumors in vivo. The purpose of this study was to determine the relative importance of two isoforms of vascular endothelial growth factor (VEGF) in tumor vessel expansion and recruitment of bone marrow-derived cells during tumor growth. We injected VEGF(165)-siRNA-transfected cells (TCsi/7-1), control siRNA-transfected cells (TC/si-control), or TC71 parental Ewing's sarcoma cells into nude mice. The TCsi/7-1 tumors were then treated with adenoviral vectors expressing VEGF(165) (Ad-VEGF(165)), VEGF(189) (Ad-VEGF(189)), or beta-galactosidase (Ad-beta-gal). Bone marrow cells labeled with fluorescent tracker dye were injected into the mice 3 weeks later. The TCsi/7-1 tumors were significantly smaller (P < 0.05), had decreased vessel density, and showed significantly lower bone marrow cell migration than did TC71 parental and TC/si-control tumors. Treatment with Ad-VEGF(165), but not Ad-VEGF(189) or Ad-beta-gal, resulted in a significant increase in bone marrow cell infiltration, tumor vessel density, and tumor growth. Immunohistochemical staining revealed that the injected bone marrow cells migrated to and incorporated into the expanding CD31(+) tumor vessel network. Taken together, these data show that VEGF(165) is a chemoattractant that recruits bone marrow cells into the tumor area. These data provide a mechanism by which Ewing's sarcoma cells induce vasculogenesis. 相似文献
108.
109.
Krishna Praveen Robinson Dale L. Bucknill Andrew Lee Peter Vee Sin 《Biomechanics and modeling in mechanobiology》2022,21(4):1317-1324
Biomechanics and Modeling in Mechanobiology - Personalised fracture plates manufactured using 3D printing offer an improved treatment option for unstable pelvic ring fractures that may not be... 相似文献
110.
Malti Arya Nidhi Mishra Pooja Singh Chandra B. Tripathi Poonam Parashar Mahendra Singh Krishna P. Gupta Shubhini A. Saraf 《Journal of cellular physiology》2019,234(9):15527-15536
Inositol hexaphosphate (IP6) is a natural constituent found in almost all cereals and legumes. It is known to cause numerous antiangiogenic manifestations. Notwithstanding its great potential, it is underutilized due to the chelation and rapid excretion from the body. Jacalin is another natural constituent obtained from seeds of jackfruit and can target disaccharides overexpressed in tumor cells. The current study was in-quested to develop and evaluate a surface-modified gold nanoparticulate system containing IP6 and jacalin which may maximize the apoptotic effect of IP6 against HCT-15 cell lines. IP6 loaded jacalin-pectin-gold nanoparticles (IJP-GNPs) were developed through reduction followed by incubation method. The developed formulation was tested for various in vitro and in silico studies to investigate its potential. HCT-15 cells when exposed to IJP-GNP resulted in significant apoptotic effects in dose as well as time-dependent manner, as measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, micronucleus, and reactive oxygen species assay. IJP-GNP displayed cell cycle arrest at the G0/G1 phase. To further explore the mechanism of chemoprevention, in silico studies were performed. The docking results revealed that the interactive behavior of IP6, P-GNP, and jacalin could target and inhibit the tumor formation activity, supported by in vitro studies. Taken together, all the findings suggested that IP6 loaded nanoparticles may increase the hope of future drug delivery strategy for targeting colon cancer. 相似文献