全文获取类型
收费全文 | 2355篇 |
免费 | 140篇 |
国内免费 | 198篇 |
专业分类
2693篇 |
出版年
2024年 | 8篇 |
2023年 | 50篇 |
2022年 | 102篇 |
2021年 | 177篇 |
2020年 | 94篇 |
2019年 | 100篇 |
2018年 | 103篇 |
2017年 | 62篇 |
2016年 | 110篇 |
2015年 | 154篇 |
2014年 | 192篇 |
2013年 | 185篇 |
2012年 | 222篇 |
2011年 | 183篇 |
2010年 | 92篇 |
2009年 | 79篇 |
2008年 | 98篇 |
2007年 | 100篇 |
2006年 | 96篇 |
2005年 | 79篇 |
2004年 | 38篇 |
2003年 | 50篇 |
2002年 | 44篇 |
2001年 | 19篇 |
2000年 | 32篇 |
1999年 | 31篇 |
1998年 | 23篇 |
1997年 | 15篇 |
1996年 | 14篇 |
1995年 | 17篇 |
1994年 | 10篇 |
1993年 | 13篇 |
1992年 | 19篇 |
1991年 | 14篇 |
1990年 | 9篇 |
1989年 | 11篇 |
1988年 | 8篇 |
1987年 | 7篇 |
1986年 | 8篇 |
1985年 | 3篇 |
1984年 | 3篇 |
1983年 | 2篇 |
1982年 | 3篇 |
1981年 | 4篇 |
1980年 | 3篇 |
1979年 | 2篇 |
1974年 | 2篇 |
1971年 | 1篇 |
1966年 | 2篇 |
排序方式: 共有2693条查询结果,搜索用时 15 毫秒
41.
蹄蝠科的核型进化:比较染色体涂色、G带和C带分析(英文) 总被引:1,自引:0,他引:1
与其姐妹科(菊头蝠科)相比,蹄蝠科的细胞遗传学研究较少。迄今为止,仅少数蹄蝠科几个物种有高分辨率的G带核型报道,且有关该科核型进化的大多数结论都是基于常规Giemsa染色研究而得。该研究利用三叶小蹄蝠的染色体特异探针,通过比较染色体涂色、G和C显带,建立了5种蹄蝠的染色体同源性图谱,并探讨了它们同源染色体间的G和C带异同。结果表明:罗伯逊易位、臂内倒位以及异染色质的扩增可能是蹄蝠科物种核型进化的主要机制。通过对这5种蹄蝠物种及其外群物种之间的同源染色体片段的比较分析,作者推测蹄蝠科的祖先核型并不像先前认为的全由端着丝粒染色体组成,而应该含有中着丝粒染色体。 相似文献
42.
AGAP1, an endosome-associated,phosphoinositide-dependent ADP-ribosylation factor GTPase-activating protein that affects actin cytoskeleton 总被引:7,自引:0,他引:7
Nie Z Stanley KT Stauffer S Jacques KM Hirsch DS Takei J Randazzo PA 《The Journal of biological chemistry》2002,277(50):48965-48975
We have identified three members of the AGAP subfamily of ASAP family ADP-ribosylation factor GTPase-activating proteins (Arf GAPs). In addition to the Arf GAP domain, these proteins contain GTP-binding protein-like, ankyrin repeat and pleckstrin homology domains. Here, we have characterized the ubiquitously expressed AGAP1/KIAA1099. AGAP1 had Arf GAP activity toward Arf1>Arf5>Arf6. Phosphatidylinositol 4,5-bisphosphate and phosphatidic acid synergistically stimulated GAP activity. As found for other ASAP family Arf GAPs, the pleckstrin homology domain was necessary for activity. Deletion of the GTP-binding protein-like domain affected lipid dependence of Arf GAP activity. In vivo effects of AGAP1 were distinct from other ASAP family Arf GAPs. Overexpressed AGAP1 induced the formation of and was associated with punctate structures containing the endocytic markers transferrin and Rab4. AP1 was redistributed from the trans-Golgi to the punctate structures. Like other ASAP family members, AGAP1 overexpression inhibited the formation of PDGF-induced ruffles. However, distinct from other ASAP family members, AGAP1 also induced the loss of actin stress fibers. Thus, AGAP1 is a phosphoinositide-dependent Arf GAP that impacts both the endocytic compartment and actin. 相似文献
43.
Gang Li Tianming Liu Jingxin Nie Lei Guo Jarema Malicki Andrew Mara Scott A Holley Weiming Xia Stephen T C Wong 《Cytometry. Part A》2007,71(10):835-845
The zebrafish has become an important vertebrate animal model for the study of developmental biology, functional genomics, and disease mechanisms. It is also being used for drug discovery. Computerized detection of blob objects has been one of the important tasks in quantitative phenotyping of zebrafish. We present a new automated method that is able to detect blob objects, such as nuclei or cells in microscopic zebrafish images. This method is composed of three key steps. The first step is to produce a diffused gradient vector field by a physical elastic deformable model. In the second step, the flux image is computed on the diffused gradient vector field. The third step performs thresholding and nonmaximum suppression based on the flux image. We report the validation and experimental results of this method using zebrafish image datasets from three independent research labs. Both sensitivity and specificity of this method are over 90%. This method is able to differentiate closely juxtaposed or connected blob objects, with high sensitivity and specificity in different situations. It is characterized by a good, consistent performance in blob object detection. 相似文献
44.
Chemically sulfated polysaccharide (S-GAP-P) was derived from water-insoluble polysaccharide of Grifola frondosa mycelia. In this research, we investigated the anticancer effects of S-GAP-P and its combination with 5-fluorouracil (5-FU) on human gastric carcinoma SGC-7901 cells. Results showed that S-GAP-P distinctly inhibited SGC-7901 cells growth in a dose-dependent manner and induced cell apoptosis evidenced by characteristic DNA ladder and sub-G0/G1 peak. Furthermore, the combination of S-GAP-P (10–50 μg/ml) with 1 μg/ml 5-FU resulted in a significant inhibition on SGC-7901 cells growth, meaning the beneficial interaction between the two drugs. All these results suggested that S-GAP-P has evident anticancer activity through apoptotic induction and could significantly accelerate the anticancer activity of 5-FU. 相似文献
45.
Small molecules blocking the entry of severe acute respiratory syndrome coronavirus into host cells 总被引:4,自引:0,他引:4 下载免费PDF全文
Yi L Li Z Yuan K Qu X Chen J Wang G Zhang H Luo H Zhu L Jiang P Chen L Shen Y Luo M Zuo G Hu J Duan D Nie Y Shi X Wang W Han Y Li T Liu Y Ding M Deng H Xu X 《Journal of virology》2004,78(20):11334-11339
Severe acute respiratory syndrome coronavirus (SARS-CoV) is the pathogen of SARS, which caused a global panic in 2003. We describe here the screening of Chinese herbal medicine-based, novel small molecules that bind avidly with the surface spike protein of SARS-CoV and thus can interfere with the entry of the virus to its host cells. We achieved this by using a two-step screening method consisting of frontal affinity chromatography-mass spectrometry coupled with a viral infection assay based on a human immunodeficiency virus (HIV)-luc/SARS pseudotyped virus. Two small molecules, tetra-O-galloyl-beta-D-glucose (TGG) and luteolin, were identified, whose anti-SARS-CoV activities were confirmed by using a wild-type SARS-CoV infection system. TGG exhibits prominent anti-SARS-CoV activity with a 50% effective concentration of 4.5 microM and a selective index of 240.0. The two-step screening method described here yielded several small molecules that can be used for developing new classes of anti-SARS-CoV drugs and is potentially useful for the high-throughput screening of drugs inhibiting the entry of HIV, hepatitis C virus, and other insidious viruses into their host cells. 相似文献
46.
Photosynthesis Research - Formation of photosynthetic complexes leads to a higher demand for Fe–S clusters. We hypothesized that in the facultative phototrophic alpha-proteobacterium... 相似文献
47.
外源氮输入对黄河口新生湿地植物-土壤系统硫分布特征的影响 总被引:2,自引:0,他引:2
选择黄河口北部滨岸高潮滩的碱蓬湿地为研究对象,基于野外原位氮(N)输入模拟试验,研究了不同氮输入梯度下(N0,无氮输入;N1,低氮输入,9.0 gN m~(-2)a~(-1);N2,中氮输入,12.0 gN m~(-2)a~(-1);N3,高氮输入,18.0 gN m~(-2)a~(-1))碱蓬湿地植物-土壤系统全硫(TS)分布特征的差异。结果表明,外源N输入明显改变了湿地土壤TS含量的分布状况。随着N输入量的增加,除表层TS含量变化不明显外,其他土层均呈增加趋势。不同氮输入处理下植物各器官的TS含量整体均表现为叶茎根,叶是硫的主要累积器官。尽管氮输入处理并未改变植被的硫分配格局以及其地上与地下之间的硫养分供给关系,但其为适应不同养分环境可进行自身生长特性及养分分配的调整,且这种调整在N2处理下表现的尤为明显。随氮输入量的增加,不同氮处理下植物-土壤系统的S储量整体呈增加趋势,但土壤S储量的增幅远低于植物亚系统S储量的增幅以及N供给的增幅,说明N、S之间的养分供给存在不同步性。研究发现,未来黄河口N养分负荷增加情况下,碱蓬湿地植物-土壤系统的S生物循环速率不但可能会加速,而且N、S养分之间也可能形成一个正反馈机制,并将有利于维持新生湿地的稳定与健康。 相似文献
48.
Xiaopeng Ji Bin Zhao Zhaoping Cheng Biao Si Zhiheng Wang Yanhua Duan Pei Nie Haiou Li Shifeng Yang Hui Jiao Ximing Wang 《PloS one》2014,9(4)
Objective
To explore the clinical value of low-dose prospectively electrocardiogram-gated axial dual-source CT angiography (low-dose PGA scanning, CTA) in patients with pulsatile bilateral bidirectional Glenn shunt (bBDG) as an alternative noninvasive method for postoperative morphological estimation.Methods
Twenty patients with pulsatile bBDG (mean age 4.2±1.6 years) underwent both low-dose PGA scanning and conventional cardiac angiography (CCA) for the morphological changes. The morphological evaluation included the anatomy of superior vena cava (SVC) and pulmonary artery (PA), the anastomotic location, thrombosis, aorto-pulmonary collateral circulation, pulmonary arteriovenous malformations, etc. Objective and subjective image quality was assessed. Bland–Altman analysis and linear regression analyses were used to evaluate the correlation on measurements between CTA and CCA. Effective radiation dose of both modalities was calculated.Results
The CT attenuation value of bilateral SVC and PA was higher than 300 HU. The average subjective image quality score was 4.05±0.69. The morphology of bilateral SVC and PA was displayed completely and intuitively by CTA images. There were 24 SVC above PA and 15 SVC beside PA. Thrombosis was found in 1 patient. Collateral vessels were detected in 13 patients. No pulmonary arteriovenous malformation was found in our study. A strong correlation (R2>0.8, P<0.001) was observed between the measurements on CTA images and on CCA images. Bland–Altman analysis demonstrated a systematic overestimation of the measurements by CTA (the mean value of bias>0).The mean effective dose of CTA and CCA was 0.50±0.17 mSv and 4.85±1.34 mSv respectively.Conclusion
CT angiography with a low-dose PGA scanning is an accurate and reliable noninvasive examination in the assessment of morphological changes in patients with pulsatile bBDG. 相似文献49.
Yoo J Rodriguez Perez CE Nie W Edwards RA Sinnett-Smith J Rozengurt E 《American journal of physiology. Gastrointestinal and liver physiology》2012,302(8):G805-G814
The myofibroblast has recently been identified as an important mediator of tumor necrosis factor-α (TNF-α)-associated colitis and cancer, but the mechanism(s) involved remains incompletely understood. Recent evidence suggests that TNF-α is a central regulator of multiple inflammatory signaling cascades. One important target of TNF-α may be the signaling pathway downstream of the epidermal growth factor receptor (EGFR), which has been associated with many human cancers. Here, we show that long-term exposure of 18Co cells, a model of human colonic myofibroblasts, with TNF-α led to a striking increase in cell surface EGFR expression, an effect that was completely inhibited by cycloheximide. Subsequent EGFR binding by EGF and heparin binding (HB)-EGF was associated with enhanced EGFR tyrosine kinase activity, prolonged ERK activation, and a significant increase in cyclooxygenase-2 (COX-2) expression compared with 18Co cells treated with EGF and HB-EGF alone. TNF-α also increased EGFR expression and signaling in primary myofibroblasts isolated from human colon tissue. TNF-α-induced upregulation of EGFR may be a plausible mechanism to explain the exaggerated cellular responsiveness that characterizes inflammatory bowel disease and that may contribute to a microenvironment that predisposes to colitis-associated cancer through enhanced COX-2 expression. 相似文献
50.
懒猴属的核糖体DNA变异及其种间分化关系 总被引:3,自引:2,他引:3
用15种限制性内切酶和人28S、18SrDNA探针构建了懒猴属各物种核糖体DNA重复单位的限制性内切酶图谱。在进化速率较高的非转录间隔区,在大、中、小懒猴中分别定位了23、24、24个酶切位点。大懒猴与中懒猴有12个位点不同,与小懒猴有14个位点不同,而中、小懒猴间则只有一个位点的差异。经过计算,大懒猴与中懒猴的遗传距离值为12.65%,与小懒猴的差异为14.24%,中、小懒猴间的差异则仅为0.7 相似文献