全文获取类型
收费全文 | 2124篇 |
免费 | 88篇 |
出版年
2024年 | 2篇 |
2023年 | 9篇 |
2022年 | 29篇 |
2021年 | 48篇 |
2020年 | 27篇 |
2019年 | 51篇 |
2018年 | 57篇 |
2017年 | 36篇 |
2016年 | 86篇 |
2015年 | 118篇 |
2014年 | 124篇 |
2013年 | 157篇 |
2012年 | 214篇 |
2011年 | 204篇 |
2010年 | 130篇 |
2009年 | 106篇 |
2008年 | 161篇 |
2007年 | 144篇 |
2006年 | 88篇 |
2005年 | 93篇 |
2004年 | 78篇 |
2003年 | 65篇 |
2002年 | 42篇 |
2001年 | 28篇 |
2000年 | 29篇 |
1999年 | 25篇 |
1998年 | 7篇 |
1997年 | 5篇 |
1996年 | 1篇 |
1995年 | 3篇 |
1994年 | 1篇 |
1993年 | 5篇 |
1992年 | 9篇 |
1991年 | 4篇 |
1989年 | 3篇 |
1988年 | 1篇 |
1986年 | 3篇 |
1985年 | 1篇 |
1983年 | 1篇 |
1982年 | 2篇 |
1981年 | 1篇 |
1980年 | 1篇 |
1976年 | 2篇 |
1975年 | 2篇 |
1973年 | 1篇 |
1970年 | 1篇 |
1969年 | 2篇 |
1968年 | 1篇 |
1967年 | 3篇 |
1965年 | 1篇 |
排序方式: 共有2212条查询结果,搜索用时 15 毫秒
941.
We have developed an off-lattice hybrid discrete-continuum (OLHDC) model of tumor growth and invasion. The continuum part of the OLHDC model describes microenvironmental components such as matrix-degrading enzymes, nutrients or oxygen, and extracellular matrix (ECM) concentrations, whereas the discrete portion represents individual cell behavior such as cell cycle, cell-cell, and cell-ECM interactions and cell motility by the often-used persistent random walk, which can be depicted by the Langevin equation. Using this framework of the OLHDC model, we develop a phenomenologically realistic and bio/physically relevant model that encompasses the experimentally observed superdiffusive behavior (at short times) of mammalian cells. When systemic simulations based on the OLHDC model are performed, tumor growth and its morphology are found to be strongly affected by cell-cell adhesion and haptotaxis. There is a combination of the strength of cell-cell adhesion and haptotaxis in which fingerlike shapes, characteristic of invasive tumor, are observed. 相似文献
942.
Bita Carrion Carlos P. Huang Cyrus M. Ghajar Suraj Kachgal Ekaterina Kniazeva Noo Li Jeon Andrew J. Putnam 《Biotechnology and bioengineering》2010,107(6):1020-1028
Stem cell niches are composed of numerous microenvironmental features, including soluble and insoluble factors, cues from other cells, and the extracellular matrix (ECM), which collectively serve to maintain stem cell quiescence and promote their ability to support tissue homeostasis. A hallmark of many adult stem cell niches is their proximity to the vasculature in vivo, a feature common to neural stem cells, mesenchymal stem cells (MSCs) from bone marrow and adipose tissue, hematopoietic stem cells, and many tumor stem cells. In this study, we describe a novel 3D microfluidic device (MFD) as a model system in which to study the molecular regulation of perivascular stem cell niches. Endothelial cells (ECs) suspended within 3D fibrin gels patterned in the device adjacent to stromal cells (either fibroblasts or bone marrow‐derived MSCs) executed a morphogenetic process akin to vasculogenesis, forming a primitive vascular plexus and maturing into a robust capillary network with hollow well‐defined lumens. Both MSCs and fibroblasts formed pericytic associations with the ECs but promoted capillary morphogenesis with distinct kinetics. Biochemical assays within the niche revealed that the perivascular association of MSCs required interaction between their α6β1 integrin receptor and EC‐deposited laminin. These studies demonstrate the potential of this physiologically relevant ex vivo model system to study how proximity to blood vessels may influence stem cell multipotency. Biotechnol. Bioeng. 2010;107: 1020–1028. © 2010 Wiley Periodicals, Inc. 相似文献
943.
Cysteamine (1) was reported many years ago to reversibly inhibit lentil seedling amine oxidase, through the formation of a complex with thioacetaldehyde, the turnover product of 1. Herein, cysteamine (1) and its analogs 2-(methylamino)ethanethiol (3) and 3-aminopropanethiol (6) were found to be reversible inhibitors of bovine plasma amine oxidase (BPAO), but 2-(methylthio)ethylamine (7) was determined to be a weak irreversible inhibitor of BPAO. Based on our results, indicating the necessity of a sulfhydryl-amine for reversible inactivation of BPAO, the failure of inhibited BPAO to recover activity after gel filtration, the first-order kinetics of activity recovery upon dialysis, and 2,4,6-trihydroxyphenylalanine quinine (TPQ) cofactor transformation which indicated from the results of phenylhydrazine titration and substrate protection, we propose a mechanism for the reversible inactivation of BPAO by 1 involving the formation of a cofactor adduct, thiazolidine, between BPAO and 1. 相似文献
944.
945.
Yong-Won Kang Jae-Yong Lee Young Jeon Gang-Won Cheong Moonil Kim Hyun-Sook Pai 《Plant molecular biology》2010,72(6):569-583
Sulfite reductase (SiR) performs dual functions, acting as a sulfur assimilation enzyme and as a chloroplast (cp-) nucleoid
binding protein. In this study, we examined the in vivo effects of SiR deficiency on chloroplast development in Nicotiana benthamiana. Virus-induced gene silencing of NbSiR resulted in leaf yellowing and growth retardation phenotypes, which were not rescued by cysteine supplementation. NbSiR:GFP
fusion protein was targeted to chloroplasts and colocalized with cp-nucleoids. Recombinant full-length NbSiR protein and the
C-terminal half of NbSiR possessed cp-DNA compaction activities in vitro, and expression of full-length NbSiR in E. coli caused condensation of genomic DNA. NbSiR silencing differentially affected expression of plastid-encoded genes, inhibiting expression of several genes more severely
than others. In the later stages, depletion of NbSiR resulted in chloroplast ablation. In NbSiR-silenced plants, enlarged cp-nucleoids containing an increased amount of cp-DNA were observed in the middle of the abnormal
chloroplasts, and the cp-DNAs were predominantly of subgenomic sizes based on pulse field gel electrophoresis. The abnormal
chloroplasts developed prolamellar body-like cubic lipid structures in the light without accumulating NADPH:protochlorophyllide
oxidoreductase proteins. Our results suggest that NbSiR plays a role in cp-nucleoid metabolism, plastid gene expression, and
thylakoid membrane development. 相似文献
946.
Eun-Ju Kim Jong-Rok Jeon Young-Mo Kim Kumarasamy Murugesan Yoon-Seok Chang 《Applied microbiology and biotechnology》2010,87(4):1569-1577
The aerobic metabolism of monofluorophenols (mono-FPs) by the actinomycete, Pseudonocardia benzenivorans, was studied. This strain was able to grow on 4-fluorophenol (4-FP) and readily transform 2- and 3-fluorophenol to the corresponding
metabolites. The detailed mechanism of mono-FPs degradation by P. benzenivorans was elucidated from enzymatic assays and the identification of reaction intermediates by high-performance liquid chromatography
(HPLC) and gas chromatography–mass spectrometry. Two types of fluorocatechols (i.e., 3- and 4-fluorocatechol) were identified
as the key transformation products. During 4-FP degradation, only 4-fluorocatechol was detected, and a stoichiometric level
of fluoride was released. Both fluorocatechols were observed together in cultures containing 3-fluorophenol (3-FP), while
only 3-fluorocatechol was found to accumulate in 2-fluorophenol (2-FP)-containing cultures. Whole-cell extracts of P. benzenivorans expressed catechol 1,2-dioxygenase activity, indicating that the transformation of the three tested mono-FPs proceeded via
ortho-cleavage pathway. The results presented in this paper provide comprehensive information regarding the metabolism of mono-FPs
by a single bacterium. 相似文献
947.
948.
In an attempt to determine the prevalence of pinworm infection, the egg positive rate of Enterobius vermicularis was examined using the adhesive cello-tape anal swab method in 1,512 preschool children sampled from a total of 20 kindergartens in Cheongju city, in November to December of 2004 (951 children from 13 kindergartens) and September to October of 2005 (561 from 7 kindergartens). The overall egg positive rate was found to be 7.9% (119/1,512); 9.3% (73/784) for boys and 6.3% (46/728) for girls, respectively. The 5-year age group evidenced the highest egg positive rate (10.9%, 47/430) among the examined age groups. As compared to those reported from previous works (ranged from 9.2 to 26.1%), the prevalence of E. vermicularis in the Cheongju city area is relatively low. 相似文献
949.
Lee HS Kim YJ Bae SS Jeon JH Lim JK Jeong BC Kang SG Lee JH 《Applied and environmental microbiology》2006,72(3):1886-1890
Genomic analysis of a hyperthermophilic archaeon, Thermococcus sp. strain NA1, revealed the presence of a 1,068-bp open reading frame encoding a protein consisting of 356 amino acids with a calculated molecular mass of 39,714 Da (GenBank accession no. DQ144132). Sequence analysis showed that it was similar to the putative aminopeptidase P (APP) of Thermococcus kodakaraensis KOD1. Amino acid residues important for catalytic activity and the metal binding ligands conserved in bacterial, nematode, insect, and mammalian APPs were also conserved in the Thermococcus sp. strain NA1 APP. The archaeal APP, designated TNA1_APP (Thermococcus sp. strain NA1 APP), was cloned and expressed in Escherichia coli. The recombinant enzyme hydrolyzed the amino-terminal Xaa-Pro bond of Lys(Nepsilon-Abz)-Pro-Pro-pNA and the dipeptide Met-Pro (Km, 0.96 mM), revealing its functional identity. Further enzyme characterization showed the enzyme to be a Co2+-, Mn2+-, or Zn2+-dependent metallopeptidase. Optimal APP activity with Met-Pro as the substrate occurred at pH 5 and a temperature of 100 degrees C. The APP was thermostable, with a half-life of >100 min at 80 degrees C. This study represents the first characterization of a hyperthermophilic archaeon APP. 相似文献
950.
Moon HJ Yim SV Lee WK Jeon YW Kim YH Ko YJ Lee KS Lee KH Han SI Rha HK 《Biochemical and biophysical research communications》2006,344(2):531-539
Chromosomal abnormalities are implicated as important markers for the pathogenesis in patients with schizophrenia. In this study, with using bacterial artificial chromosome (BAC) array-based comparative genomic hybridization (CGH), we analyzed DNA copy-number changes among 30 patients with schizophrenia. The most frequent changes were partial gain of Xq23 (52%) and loss of 3q13.12 (32%). Other frequent gains were found in: 1p, 6q, 10p, 11p, 11q, 14p, and 15q regions, and frequent losses were found in: 2p, 9q, 10q, 14q, 20q, and 22q regions. The set of abnormal regions was confirmed by real-time PCR (9q12, 9q34.2, 11p15.4, 14q32.33, 15q15.1, 22q11.21, and Xq23). All real-time PCR results were consistent with the array-CGH results. Therefore, it is suggested that array-CGH and real-time PCR analysis could be used as powerful tools in screening for schizophrenia-related genes. Our results might be useful for further exploration of candidate genomic regions in the pathogenesis of schizophrenia. 相似文献