全文获取类型
收费全文 | 5466篇 |
免费 | 556篇 |
国内免费 | 1059篇 |
出版年
2024年 | 24篇 |
2023年 | 57篇 |
2022年 | 153篇 |
2021年 | 263篇 |
2020年 | 206篇 |
2019年 | 250篇 |
2018年 | 225篇 |
2017年 | 174篇 |
2016年 | 275篇 |
2015年 | 358篇 |
2014年 | 475篇 |
2013年 | 472篇 |
2012年 | 595篇 |
2011年 | 491篇 |
2010年 | 364篇 |
2009年 | 344篇 |
2008年 | 376篇 |
2007年 | 377篇 |
2006年 | 287篇 |
2005年 | 256篇 |
2004年 | 226篇 |
2003年 | 182篇 |
2002年 | 160篇 |
2001年 | 77篇 |
2000年 | 62篇 |
1999年 | 84篇 |
1998年 | 62篇 |
1997年 | 27篇 |
1996年 | 32篇 |
1995年 | 21篇 |
1994年 | 24篇 |
1993年 | 17篇 |
1992年 | 16篇 |
1991年 | 12篇 |
1990年 | 5篇 |
1989年 | 5篇 |
1988年 | 4篇 |
1987年 | 5篇 |
1986年 | 6篇 |
1985年 | 4篇 |
1984年 | 2篇 |
1982年 | 5篇 |
1981年 | 3篇 |
1977年 | 2篇 |
1972年 | 2篇 |
1967年 | 1篇 |
1961年 | 1篇 |
1950年 | 4篇 |
1925年 | 1篇 |
1915年 | 1篇 |
排序方式: 共有7081条查询结果,搜索用时 15 毫秒
921.
Background
Compressive mechanical stress produced during growth in a confining matrix limits the size of tumor spheroids, but little is known about the dynamics of stress accumulation, how the stress affects cancer cell phenotype, or the molecular pathways involved.Methodology/Principal Findings
We co-embedded single cancer cells with fluorescent micro-beads in agarose gels and, using confocal microscopy, recorded the 3D distribution of micro-beads surrounding growing spheroids. The change in micro-bead density was then converted to strain in the gel, from which we estimated the spatial distribution of compressive stress around the spheroids. We found a strong correlation between the peri-spheroid solid stress distribution and spheroid shape, a result of the suppression of cell proliferation and induction of apoptotic cell death in regions of high mechanical stress. By compressing spheroids consisting of cancer cells overexpressing anti-apoptotic genes, we demonstrate that mechanical stress-induced apoptosis occurs via the mitochondrial pathway.Conclusions/Significance
Our results provide detailed, quantitative insight into the role of micro-environmental mechanical stress in tumor spheroid growth dynamics, and suggest how tumors grow in confined locations where the level of solid stress becomes high. An important implication is that apoptosis via the mitochondrial pathway, induced by compressive stress, may be involved in tumor dormancy, in which tumor growth is held in check by a balance of apoptosis and proliferation. 相似文献922.
GLay: community structure analysis of biological networks 总被引:1,自引:0,他引:1
SUMMARY: GLay provides Cytoscape users an assorted collection of versatile community structure algorithms and graph layout functions for network clustering and structured visualization. High performance is achieved by dynamically linking highly optimized C functions to the Cytoscape JAVA program, which makes GLay especially suitable for decomposition, display and exploratory analysis of large biological networks. AVAILABILITY: http://brainarray.mbni.med.umich.edu/glay/. 相似文献
923.
Kyogashima M Tamiya-Koizumi K Ehara T Li G Hu R Hara A Aoyama T Kannagi R 《Glycobiology》2006,16(8):719-728
By combining the partition method for enrichment of sulfatides without any chromatographic procedures and the preparation method of lysosulfatides, we succeeded in analyzing these sulfated glycosphingolipids from biological materials by matrix-assisted laser desorption and ionization time-of-flight mass spectrometry (MALDI-TOF MS) to reduce the complexity of mass fragmentation patterns within a day. We found that sulfated GalCer (HSO3-3Gal beta 1Cer) (SM4s [galactosylsulfatide]) was composed of different species. While composition of SM4s specifically depended on source materials, it always contained hydroxy fatty acids of various degrees. In addition to the common sphingoid 4-sphingenine (d18:1), uncommon/unusual sphingoids phytosphingosine (4-hydroxysphinganine) (t18:0), eicosasphinganine (d20:0), 4-eicosasphingenine (d20:1), and sphingadienine (d18:2) were easily detected. Finally, in addition to SM4s, sulfatide sulfated LacCer (HSO3-3Gal beta 4Glc beta 1Cer) (SM3 [sulfated lactosylceramide]) and sulfated Gg3Cer (GalNAc beta 4(HSO3-3)Gal beta 4Glc beta 1Cer) (SM2 [sulfated gangliotriaosylceramide]) were clearly detected in renal tubule cells. The major SM4s was composed of ceramides possessing d18:1 with C22 hydroxy fatty acids (C22:0 h), C23:0 h, and C24:0 h, whereas the major SM3/SM2 were composed of ceramides possessing t18:0 with C22 normal fatty acids (C22:0), C23:0, C24:0. Namely, in these two series of sulfatides, either fatty acids or sphingoids were hydroxylated, and chain lengths of these components were exactly the same, consequently resulting in a similar polarity of ceramide moieties in these sulfatide species. These results demonstrated diversities of sulfatide molecular species, not only with respect to sugar moieties but also to ceramide moieties, which are probably important for specific effective functions in particular microenvironments such as lipid membrane microdomains. 相似文献
924.
Yin Z Patel SJ Wang WL Chan WL Ranga Rao KR Wang G Ngew X Patel V Beer D Knox JE Ma NL Ehrhardt C Lim SP Vasudevan SG Keller TH 《Bioorganic & medicinal chemistry letters》2006,16(1):40-43
With the aim of discovering potent and selective dengue NS3 protease inhibitors, we systematically synthesized and evaluated a series of tetrapeptide aldehydes based on lead aldehyde 1 (Bz-Nle-Lys-Arg-Arg-H, K(i)=5.8 microM). In general, we observe that interactions of P(2) side chain are more important than P(1) followed by P(3) and P(4). Tripeptide and dipeptide aldehyde inhibitors also show low micromolar activity. Additionally, an effective non-basic, uncharged replacement of P(1) Arg is identified. 相似文献
925.
Hydrophobicity analyses applied to databases of soluble and transmembrane (TM) proteins of known structure were used to resolve total genomic hydrophobicity profiles into (helical) TM sequences and mainly "subhydrophobic" soluble components. This information was used to define a refined "hydrophobicity"-type TM sequence prediction scale that should approach the theoretical limit of accuracy. The refinement procedure involved adjusting scale values to eliminate differences between the average amino acid composition of populations TM and soluble sequences of equal hydrophobicity, a required property of a scale having maximum accuracy. Application of this procedure to different hydrophobicity scales caused them to collapse to essentially a single TM tendency scale. As expected, when different scales were compared, the TM tendency scale was the most accurate at predicting TM sequences. It was especially highly correlated (r = 0.95) to the biological hydrophobicity scale, derived experimentally from the percent TM conformation formed by artificial sequences passing though the translocon. It was also found that resolution of total genomic sequence data into TM and soluble components could be used to define the percent probability that a sequence with a specific hydrophobicity value forms a TM segment. Application of the TM tendency scale to whole genomic data revealed an overlap of TM and soluble sequences in the "semihydrophobic" range. This raises the possibility that a significant number of proteins have sequences that can switch between TM and non-TM states. Such proteins may exist in moonlighting forms having properties very different from those of the predominant conformation. 相似文献
926.
番茄碱对棉铃虫的毒性作用机理初探 总被引:2,自引:0,他引:2
采取荧光光谱法分析了番茄碱及虫体内钙调蛋白的图谱,从钙调蛋白的角度探讨了番茄碱的作用机理.结果显示:(1)番茄碱对棉铃虫具有毒性,随浓度的增加及饲喂时间的延长,对棉铃虫的杀伤力增强;(2)番茄碱对虫体内钙调蛋白的影响较大,随番茄碱浓度的增加,钙调蛋白的含量逐渐降低;(3)钙离子的加入增强了钙调蛋白的刚性,荧光图谱出现了红移(由350 nm移至416.58 nm);(4)番茄碱的加入破坏了钙调蛋白-钙离子复合物的刚性,荧光图谱出现了蓝移(416.58 nm移至377.65 nm).以上可以说明,番茄碱可能作为钙调蛋白的拮抗剂,拮抗钙调蛋白被钙离子激活的位点,影响其与靶酶的结合而发挥作用.此项的研究为探讨番茄碱的杀虫机理提供了科学依据. 相似文献
927.
目的:建立红色荧光蛋白在里氏木霉中的表达方法,为深入研究里氏木霉中纤维素酶的合成机理打下基础。方法:采用PCR方法分离了里氏木霉纤维二糖水解酶Ⅰ(CBHⅠ)的启动子(Pcbh1)和终止序列(Tcbh1),将这两个片段与红色荧光蛋白(DsRed)的基因连接,得到Pcbh1-DsRed-Tcbh1表达盒。用此表达盒和质粒pAN7-1对里氏木霉QM9414的原生质体进行共转化,并用含100μg/ml潮霉素B的选择性平板进行筛选。结果:经筛选得到20个抗性转化子,在乳糖的诱导下有5个转化子可以表达红色荧光蛋白。对插入片段进行了扩增和序列测定,结果表明DsRed通过同源重组整合到了转化子的基因组DNA上,并处于cbh1启动子的下游。结论:通过cbh1启动子可以实现红色荧光蛋白在里氏木霉细胞内的稳定表达。 相似文献
928.
929.
930.
Eakin CM Morgan JA Heron SF Smith TB Liu G Alvarez-Filip L Baca B Bartels E Bastidas C Bouchon C Brandt M Bruckner AW Bunkley-Williams L Cameron A Causey BD Chiappone M Christensen TR Crabbe MJ Day O de la Guardia E Díaz-Pulido G DiResta D Gil-Agudelo DL Gilliam DS Ginsburg RN Gore S Guzmán HM Hendee JC Hernández-Delgado EA Husain E Jeffrey CF Jones RJ Jordán-Dahlgren E Kaufman LS Kline DI Kramer PA Lang JC Lirman D Mallela J Manfrino C Maréchal JP Marks K Mihaly J Miller WJ Mueller EM 《PloS one》2010,5(11):e13969