全文获取类型
收费全文 | 29170篇 |
免费 | 2128篇 |
国内免费 | 1614篇 |
专业分类
32912篇 |
出版年
2024年 | 64篇 |
2023年 | 345篇 |
2022年 | 834篇 |
2021年 | 1416篇 |
2020年 | 965篇 |
2019年 | 1191篇 |
2018年 | 1169篇 |
2017年 | 833篇 |
2016年 | 1229篇 |
2015年 | 1895篇 |
2014年 | 2126篇 |
2013年 | 2290篇 |
2012年 | 2613篇 |
2011年 | 2289篇 |
2010年 | 1452篇 |
2009年 | 1237篇 |
2008年 | 1512篇 |
2007年 | 1329篇 |
2006年 | 1166篇 |
2005年 | 982篇 |
2004年 | 790篇 |
2003年 | 695篇 |
2002年 | 533篇 |
2001年 | 479篇 |
2000年 | 379篇 |
1999年 | 411篇 |
1998年 | 243篇 |
1997年 | 265篇 |
1996年 | 252篇 |
1995年 | 214篇 |
1994年 | 217篇 |
1993年 | 150篇 |
1992年 | 216篇 |
1991年 | 184篇 |
1990年 | 130篇 |
1989年 | 106篇 |
1988年 | 79篇 |
1987年 | 108篇 |
1986年 | 82篇 |
1985年 | 69篇 |
1984年 | 52篇 |
1983年 | 36篇 |
1982年 | 36篇 |
1981年 | 26篇 |
1980年 | 21篇 |
1979年 | 25篇 |
1978年 | 17篇 |
1975年 | 21篇 |
1974年 | 18篇 |
1972年 | 17篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
171.
Multivariate phenotypes may be characterized collectively by a variety of low level traits, such as in the diagnosis of a disease that relies on multiple disease indicators. Such multivariate phenotypes are often used in genetic association studies. If highly heritable components of a multivariate phenotype can be identified, it can maximize the likelihood of finding genetic associations. Existing methods for phenotype refinement perform unsupervised cluster analysis on low-level traits and hence do not assess heritability. Existing heritable component analytics either cannot utilize general pedigrees or have to estimate the entire covariance matrix of low-level traits from limited samples, which leads to inaccurate estimates and is often computationally prohibitive. It is also difficult for these methods to exclude fixed effects from other covariates such as age, sex and race, in order to identify truly heritable components. We propose to search for a combination of low-level traits and directly maximize the heritability of this combined trait. A quadratic optimization problem is thus derived where the objective function is formulated by decomposing the traditional maximum likelihood method for estimating the heritability of a quantitative trait. The proposed approach can generate linearly-combined traits of high heritability that has been corrected for the fixed effects of covariates. The effectiveness of the proposed approach is demonstrated in simulations and by a case study of cocaine dependence. Our approach was computationally efficient and derived traits of higher heritability than those by other methods. Additional association analysis with the derived cocaine-use trait identified genetic markers that were replicated in an independent sample, further confirming the utility and advantage of the proposed approach. 相似文献
172.
Kim MK Kim SD Lee HY Lee SY Shim JW Yun J Kim JM Min do S Yoo YH Bae YS 《FEBS letters》2008,582(23-24):3379-3384
The collagen-binding motif (CBM) peptide, a cleavage product of osteopontin (OPN), stimulated intracellular calcium increase in human neutrophils. CBM peptide-stimulated calcium was inhibited by pertussis toxin (PTX), suggesting the influence of PTX-sensitive G-proteins. In addition CBM peptide stimulated the chemotactic migration of human neutrophils and human monocytes. CBM peptide-induced neutrophil chemotaxis was completely inhibited by PTX, once again indicating the influence of Gi proteins. CBM peptide was also found to induce mitogen activated protein kinase activation. CBM peptide-induced neutrophil chemotaxis was mediated by p38 kinase as well as an extracellular signal-regulated protein kinase. Taken together, the results suggest that a cleavage product of OPN, CBM peptide, initiates immune responses by inducing neutrophil trafficking via certain PTX-sensitive cell surface receptors. 相似文献
173.
摘要:【目的】GX0101是一株插入了禽网状内皮组织增生症病毒(REV)-LTR片段的马立克氏病毒(MDV)重组野毒株,本文将其致病性、致肿瘤性和横向传播能力与超强毒参考株(vvMd5)进行比较。【方法】利用MDV特异性核酸探针对同罩饲养的对照鸡的羽毛囊DNA进行检测。【结果】在经抗MDV疫苗免疫的SPF鸡攻毒试验中表明,GX0101株的致死率28.6%和致肿瘤率7.1%均低于超强毒参考株Md5的致死率63.1%和致肿瘤率19.0%。但是,利用MDV特异性核酸探针对同罩饲养的对照鸡的羽毛囊DNA检测表明, 相似文献
174.
Aspland SE Ballatore C Castillo R Desharnais J Eustaquio T Goelet P Guo Z Li Q Nelson D Sun C Castellino AJ Newman MJ 《Bioorganic & medicinal chemistry letters》2006,16(19):5194-5198
In the present work, we explore the possibility of introducing selectivity to existing chemotherapeutics via the design of non-pro-drug, bi-functional molecules comprising a microtubule-binding agent and a substrate for a disease-associated kinase. The design, synthesis, and in vitro biological evaluation of paclitaxel-thymidine and vinblastine-thymidine bi-functional conjugates are reported here. This work provides the first account of 'kinase-mediated trapping' of cancer therapeutics. 相似文献
175.
Tao Tan Jun Wu Chenyang Si Shaoxing Dai Youyue Zhang Nianqin Sun E Zhang Honglian Shao Wei Si Pengpeng Yang Hong Wang Zhenzhen Chen Ran Zhu Yu Kang Reyna Hernandez-Benitez Llanos Martinez Martinez Estrella Nuñez Delicado W. Travis Berggren Juan Carlos Izpisua Belmonte 《Cell》2021,184(8):2020-2032.e14
176.
Janet Lee Jeong-Hwa Baek Kyu-Sil Choi Hyun-Soo Kim Hye-Young Park Geun-Hyoung Ha Ho Park Kyo-Won Lee Chang Geun Lee Dong-Yun Yang Hyo Eun Moon Sun Ha Paek Chang-Woo Lee 《Cell cycle (Georgetown, Tex.)》2013,12(3):442-451
Multipotent mesenchymal stem/stromal cells (MSCs) are capable of differentiating into a variety of cell types from different germ layers. However, the molecular and biochemical mechanisms underlying the transdifferentiation of MSCs into specific cell types still need to be elucidated. In this study, we unexpectedly found that treatment of human adipose- and bone marrow-derived MSCs with cyclin-dependent kinase (CDK) inhibitor, in particular CDK4 inhibitor, selectively led to transdifferentiation into neural cells with a high frequency. Specifically, targeted inhibition of CDK4 expression using recombinant adenovial shRNA induced the neural transdifferentiation of human MSCs. However, the inhibition of CDK4 activity attenuated the syngenic differentiation of human adipose-derived MSCs. Importantly, the forced regulation of CDK4 activity showed reciprocal reversibility between neural differentiation and dedifferentiation of human MSCs. Together, these results provide novel molecular evidence underlying the neural transdifferentiation of human MSCs; in addition, CDK4 signaling appears to act as a molecular switch from syngenic differentiation to neural transdifferentiation of human MSCs. 相似文献
177.
Meng Sun Jing Ren Hui Du Yanmin Zhang Jie Zhang Sicen Wang Langchong He 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2010,878(28):2712-2718
We have developed an online analytical method that combines A431 cell membrane chromatography (A431/CMC) with high performance liquid chromatography and mass spectrometry (LC/MS) for identifying active components from Radix Caulophylli acting on human EGFR. Retention fractions on A431/CMC model were captured onto an enrichment column and the components were directly analyzed by combining a 10-port column switcher with an LC/MS system for separation and preliminary identification. Using Sorafenib tosylate as a positive control, taspine and caulophine from Radix Caulophylli were identified as the active molecules which could act on the EGFR. This A431/CMC-online-LC/MS method can be applied for screening active components acting on EGFR from traditional Chinese medicines exemplified by Radix Caulophylli and will be of great utility in drug discovery using natural medicinal herbs as a source of novel compounds. 相似文献
178.
Yibao Ma Yuanxi Xu Bryan D. Yestrepsky Roderick J. Sorenson Meng Chen Scott D. Larsen Hongmin Sun 《PloS one》2012,7(10)
Staphylococcus aureus is a major human pathogen and one of the more prominent pathogens causing biofilm related infections in clinic. Antibiotic resistance in S. aureus such as methicillin resistance is approaching an epidemic level. Antibiotic resistance is widespread among major human pathogens and poses a serious problem for public health. Conventional antibiotics are either bacteriostatic or bacteriocidal, leading to strong selection for antibiotic resistant pathogens. An alternative approach of inhibiting pathogen virulence without inhibiting bacterial growth may minimize the selection pressure for resistance. In previous studies, we identified a chemical series of low molecular weight compounds capable of inhibiting group A streptococcus virulence following this alternative anti-microbial approach. In the current study, we demonstrated that two analogs of this class of novel anti-virulence compounds also inhibited virulence gene expression of S. aureus and exhibited an inhibitory effect on S. aureus biofilm formation. This class of anti-virulence compounds could be a starting point for development of novel anti-microbial agents against S. aureus. 相似文献
179.
Jost B. Jonas Shefali B. Jonas Rahul A. Jonas Leonhard Holbach Yi Dai Xinghuai Sun Songhomitra Panda-Jonas 《PloS one》2012,7(10)
Background
To examine histomorphometrically the parapapillary region in human eyes.Methodology/Principal Findings
The histomorphometric study included 65 human globes (axial length:21–37 mm). On anterior-posterior histological sections, we measured the distance Bruch''s membrane end (BME)-optic nerve margin (“Gamma zone”), BME-retinal pigment epithelium (RPE) (“Beta zone”), BME-beginning of non-occluded choriocapillaris, and BME-beginning of photoreceptor layer. “Delta zone” was defined as part of gamma zone in which blood vessels of at least 50 µm diameter were not present over a length of >300 µm. Beta zone (mean length:0.35±0.52 mm) was significantly (P = 0.01) larger in the glaucoma group than in the non-glaucomatous group. It was not significantly (P = 0.28) associated with axial length. Beta zone was significantly (P = 0.004) larger than the region with occluded choriocapillaris. Gamma zone (mean length:0.63±1.25 mm) was associated with axial length (P<0.001;r2 = 0.73) with an increase starting at an axial length of 26.5 mm. It was not significantly (P = 0.24) associated with glaucomatous optic neuropathy. Delta zone (present only in eyes with axial length of ≥27 mm) was associated with axial length (P = 0.001) and scleral flange length (P<0.001) but not with glaucoma (P = 0.73).Conclusions/Significance
Parapapillary gamma zone (peripapillary sclera without overlying choroid, Bruch''s membrane and deep retinal layers) was related with axial globe elongation and was independent of glaucoma. Delta zone (no blood vessels >50 µm diameter within gamma zone) was present only in highly axially elongated globes and was not related with glaucoma. Beta zone (Bruch''s membrane without RPE) was correlated with glaucoma but not with globe elongation. Since the region with occluded choriocapillaris was smaller than beta zone, complete loss of RPE may have occurred before complete choriocapillaris closure. 相似文献180.
Clostridium tunisiense is a Gram-positive, obligate anaerobe that was first isolated in an anaerobic evironment under eutrophication. Here we report the first genome sequence of the Clostridium tunisiense TJ isolated from drain sediment of a pesticide factory in Tianjin, China. The genome is of great importance for both basic and application research. 相似文献