全文获取类型
收费全文 | 4376篇 |
免费 | 375篇 |
国内免费 | 118篇 |
专业分类
4869篇 |
出版年
2024年 | 13篇 |
2023年 | 61篇 |
2022年 | 119篇 |
2021年 | 162篇 |
2020年 | 150篇 |
2019年 | 185篇 |
2018年 | 161篇 |
2017年 | 104篇 |
2016年 | 98篇 |
2015年 | 187篇 |
2014年 | 335篇 |
2013年 | 328篇 |
2012年 | 288篇 |
2011年 | 431篇 |
2010年 | 286篇 |
2009年 | 199篇 |
2008年 | 228篇 |
2007年 | 210篇 |
2006年 | 204篇 |
2005年 | 159篇 |
2004年 | 169篇 |
2003年 | 127篇 |
2002年 | 91篇 |
2001年 | 63篇 |
2000年 | 63篇 |
1999年 | 55篇 |
1998年 | 50篇 |
1997年 | 37篇 |
1996年 | 47篇 |
1995年 | 48篇 |
1994年 | 46篇 |
1993年 | 28篇 |
1992年 | 19篇 |
1991年 | 23篇 |
1990年 | 8篇 |
1989年 | 9篇 |
1988年 | 3篇 |
1987年 | 6篇 |
1986年 | 5篇 |
1985年 | 10篇 |
1984年 | 19篇 |
1983年 | 9篇 |
1982年 | 10篇 |
1981年 | 5篇 |
1980年 | 2篇 |
1979年 | 3篇 |
1977年 | 2篇 |
1976年 | 1篇 |
1975年 | 1篇 |
1974年 | 1篇 |
排序方式: 共有4869条查询结果,搜索用时 15 毫秒
21.
pH-responsive nanoparticles (NPs) are currently under intense development as drug delivery systems for cancer therapy. Among various pH-responsiveness, NPs that are designed to target slightly acidic extracellular pH environment (pHe) of solid tumors provide a new paradigm of tumor targeted drug delivery. Compared to conventional specific surface targeting approaches, the pHe-targeting strategy is considered to be more general due to the common occurrence of acidic microenvironment in solid tumors. This review mainly focuses on the design and applications of pHe-activated NPs, with special emphasis on pHe-activated surface charge reversal NPs, for drug and siRNA delivery to tumors. The novel development of NPs described here offers great potential for achieving better therapeutic effects in cancer treatment. 相似文献
22.
23.
24.
目的研究肝素酶(Heparanase,Hpa)表达水平与人类肿瘤转移的相关性。方法利用半定量RT-PCR、免疫组织化学(S-P法)和Westernblot检测2组4种不同转移潜能的人类肿瘤细胞系中HpamRNA和蛋白的表达水平。结果HpamRNA和蛋白相对表达量在高转移潜能人类肺癌细胞(0·757±0·033,0·670±0·020)、乳腺癌细胞(0·617±0·024,0·661±0·013)中明显高于相应的低转移潜能肺癌细胞(0·518±0·012,0·406±0·012)、乳腺癌细胞(0·170±0·016,0·227±0·011)。结论在所研究的人类肿瘤中,HpamRNA和蛋白的表达水平与肿瘤的转移能力呈正相关。 相似文献
25.
The Blood Platelet as a Model for Regulating Blood Coagulation on Cell Surfaces and Its Consequences 总被引:2,自引:0,他引:2
Ofosu FA 《Biochemistry. Biokhimii?a》2002,67(1):47-55
Platelets actively participate in regulating thrombin production following physical or chemical injury to blood vessels. Injury to blood vessels initiates activation of the large numbers of platelets that appear in the subendothelium where they become exposed to tissue factor and to molecules adhesive for platelets and normally found in the extracellular matrix. The complex of plasma factor VIIa with extravascular tissue factor both initiates and localizes thrombin production on platelets and on extravascular cells. Thrombin production at these sites in turn enhances platelet activation and the subsequent hemostatic plug formation to minimize bleeding. Thrombin production and platelet activation also initiate the process of wound healing requiring thrombin-dependent cell activation and platelet-dependent formation of new blood vessels (angiogenesis). Activated platelets release from their storage granules several proteins and other factors that regulate local thrombin formation and the responses of blood vessel cells to injury to assure hemostasis and effective wound healing. Failure to localize and adequately regulate thrombin production and/or platelet activation can have pathological consequences, including the development and propagation of atherosclerosis and enhancement of tumor development. The primary basis for the pathological consequences of the failure to adequately regulate thrombin production is that the multi-functional thrombin activates several types of cells to initiate their mitogenesis. Mitogenesis precedes many of the undesirable consequences of poorly regulated thrombin production and platelet activation. In addition, activated platelets release a variety of products which influence the functions of several cell types to the extent that inadequate regulation of platelet activation (by excessive thrombin production) could contribute to the pathogenesis of acute and chronic arterial thrombosis and to tumor development. Activated platelets participate in tumor development by releasing several factors that positively (and negatively) regulate blood vessel formation. 相似文献
26.
27.
Prachi Jain Somesh Baranwal Shengli Dong Amanda P. Struckhoff Rebecca A. Worthylake Suresh K. Alahari 《The Journal of biological chemistry》2013,288(22):15495-15509
Biallelic inactivation of LKB1, a serine/threonine kinase, has been detected in 30% of lung adenocarcinomas, and inhibition of breast tumor growth has been demonstrated. We have identified the tumor suppressor, Nischarin, as a novel binding partner of LKB1. Our mapping analysis shows that the N terminus of Nischarin interacts with amino acids 44–436 of LKB1. Time lapse microscopy and Transwell migration data show that the absence of both Nischarin and LKB1 from an invasive breast cancer cell line (MDA-MB-231) enhances migration as measured by increased distance and speed of migrating cells. Our data suggest that this is a result of elevated PAK1 and LIMK1 phosphorylation. Moreover, the absence of Nischarin and LKB1 increased tumor growth in vivo. Consistent with this, the percentage of S phase cells was increased, as demonstrated by flow cytometry and enhanced cyclin D1. The absence of Nischarin and LKB1 also led to a dramatic increase in the formation of lung metastases. Our studies, for the first time, demonstrate functional interaction between LKB1 and Nischarin to inhibit cell migration and breast tumor progression. Mechanistically, we show that these two proteins together regulate PAK-LIMK-Cofilin and cyclin D1/CDK4 pathways. 相似文献
28.
《Cell Adhesion & Migration》2013,7(6):535-540
Angiogenesis involves a series of tightly regulated cellular processes initiated primarily by the vascular endothelial growth factor (VEGF). The urokinase-type plasminogen activator system, consisting of the urokinase-type plasminogen activator (uPA), its cellular receptor uPAR and its inhibitor PAI-1, participates in the realization of these VEGF-induced processes by activating pericellular proteolysis, increasing vascular permeability and by supporting endothelial cell proliferation and migration. 相似文献
29.
Human leptin induces angiogenesis in vivo 总被引:1,自引:0,他引:1
Anagnostoulis S Karayiannakis AJ Lambropoulou M Efthimiadou A Polychronidis A Simopoulos C 《Cytokine》2008,42(3):353-357
Leptin is an adipocyte-produced peptide, which plays a crucial role in the regulation of body weight. There is also evidence that leptin stimulates endothelial cell proliferation and the formation of capillary-like tubes in vitro. The disc angiogenesis system was used to measure the angiogenic effect of leptin in vivo. Discs containing 25, 50, 100 and 250 ng/ml of leptin were implanted subcutaneously in Wistar rats, removed after a growth period of 7 and 14 days, and compared with spontaneous growth controls and with positive controls containing equivalent doses of vascular endothelial growth factor (VEGF). Discs were examined morphologically for stroma and vessel development and by immunohistochemistry for quantitative evaluation of angiogenesis. The specificity of the angiogenic effect of leptin was tested by blocking leptin with a polyclonal anti-leptin antibody. Leptin induced a significant level of angiogenesis in a dose-dependent manner both at 7 and 14 days, with a peak at the dose of 100 ng/ml. The angiogenic activity of leptin was completely abolished by the anti-leptin neutralizing antibody. VEGF also induced significant dose-dependent angiogenesis at the same time points with a peak observed at a concentration of 100 ng/ml. The angiogenic response to leptin was significantly higher at 7 days compared with VEGF but not at the 14-day time point. In conclusion, leptin has a specific angiogenic effect in vivo, which is dose- and time-dependent in a concentration range of 25–250 ng/ml. This effect is equivalent to the angiogenic effect of VEGF but is evident earlier compared with VEGF. 相似文献
30.
The tumor suppressor p53 is believed to play an essential role in maintaining genome stability. Although it is currently unknown how p53 is involved in this important biological safeguard, several previous publications indicate that p53 can help to maintain genome integrity through the recombination-mediated DNA repair process. The integration of linearized plasmid DNA into the host chromosome utilizes the same repair process, and the frequency can be measured by clonogenic assays in which cells that were stably transfected by plasmid integration can be scored by their colony-forming abilities. To gain insight into whether p53 has a direct role in plasmid integration into the host chromosome, we determined the frequency of stable transfection with CHO cells expressing either wild-type or mutant p53 in the presence and absence of irradiation. We found that low-dose irradiation (50 to 100 cGy) increased stable transfection frequencies in CHO cells regardless of their p53 status. However, the increase of transfection frequency was significantly lower in CHO cells expressing wild-type p53. Our data thus suggest that wild-type p53 can suppress plasmid DNA integration into the host genome. This p53 function may play a direct and significant role in maintaining genome stability. 相似文献