全文获取类型
收费全文 | 3219篇 |
免费 | 233篇 |
国内免费 | 1篇 |
出版年
2023年 | 26篇 |
2022年 | 55篇 |
2021年 | 124篇 |
2020年 | 61篇 |
2019年 | 92篇 |
2018年 | 73篇 |
2017年 | 69篇 |
2016年 | 125篇 |
2015年 | 194篇 |
2014年 | 199篇 |
2013年 | 219篇 |
2012年 | 285篇 |
2011年 | 235篇 |
2010年 | 146篇 |
2009年 | 122篇 |
2008年 | 144篇 |
2007年 | 139篇 |
2006年 | 144篇 |
2005年 | 136篇 |
2004年 | 121篇 |
2003年 | 121篇 |
2002年 | 107篇 |
2001年 | 13篇 |
2000年 | 18篇 |
1999年 | 18篇 |
1998年 | 21篇 |
1997年 | 17篇 |
1996年 | 21篇 |
1995年 | 15篇 |
1994年 | 13篇 |
1993年 | 14篇 |
1992年 | 12篇 |
1991年 | 8篇 |
1990年 | 21篇 |
1989年 | 14篇 |
1988年 | 9篇 |
1987年 | 11篇 |
1986年 | 7篇 |
1985年 | 21篇 |
1984年 | 23篇 |
1983年 | 14篇 |
1982年 | 14篇 |
1981年 | 15篇 |
1980年 | 14篇 |
1973年 | 11篇 |
1972年 | 8篇 |
1968年 | 7篇 |
1967年 | 8篇 |
1963年 | 10篇 |
1959年 | 6篇 |
排序方式: 共有3453条查询结果,搜索用时 15 毫秒
891.
892.
893.
Spitz F Benbacer L Sabourin JC Salminen M Chen F Cywiner C Kahn A Chatelet F Maire P Daegelen D 《Differentiation; research in biological diversity》2002,70(8):457-467
We have previously shown that the proximal sequences of the human aldolase A fast-muscle-specific promoter (pM) are sufficient to target the expression of a linked CAT reporter gene to all fast, glycolytic trunk and limb muscles of transgenic mice (pM310CAT lines) in a manner mimicking the activity of the endogenous mouse promoter. When a NF1-binding site (motif M2) in this proximal regulatory region is mutated, the activity of the corresponding mM2 transgene is strongly affected but only in a some fast muscles. Here we show that the mutation of the M2 motif has only mild effects on pM activity in axial and proximal limb, while it drastically reduces this activity in both fore and hind limb distal muscles. At the cellular level, we show that both the pM310CAT and mM2 transgenes are highly expressed in fast glycolytic 2B fibers. However, by contrast to the pM310CAT transgene, whose expression is mainly restricted to fast glycolytic 2B fibers, the mM2 transgene is also active in a high proportion of 2X fibers. This result suggests that the M2 sequence could play a role in restricting the expression of pM to the 2B fibers. The variable expression of the mM2 transgene along the limb axis already exists at post-natal day 10 and seems to result from a change in the proportion of expressing fast fibers per muscle. Altogether, these results suggest that, although considered as phenotypically similar, different populations of fast glycolytic fibers exist, in which the requirement of the NF1 activity for pM expression varies according to the proximal versus distal position of the muscle along the limb axis. 相似文献
894.
Mammalian melatonin receptors: molecular biology and signal transduction 总被引:22,自引:0,他引:22
895.
Investigating the structural basis of purine specificity in the structures of MS2 coat protein RNA translational operator hairpins
下载免费PDF全文
![点击此处可从《Nucleic acids research》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Helgstrand C Grahn E Moss T Stonehouse NJ Tars K Stockley PG Liljas L 《Nucleic acids research》2002,30(12):2678-2685
We have determined the structures of complexes between the phage MS2 coat protein and variants of the replicase translational operator in order to explore the sequence specificity of the RNA–protein interaction. The 19-nt RNA hairpins studied have substitutions at two positions that have been shown to be important for specific binding. At one of these positions, –10, which is a bulged adenosine (A) in the stem of the wild-type operator hairpin, substitutions were made with guanosine (G), cytidine (C) and two non-native bases, 2-aminopurine (2AP) and inosine (I). At the other position, –7 in the hairpin loop, the native adenine was substituted with a cytidine. Of these, only the G-10, C-10 and C-7 variants showed interpretable density for the RNA hairpin. In spite of large differences in binding affinities, the structures of the variant complexes are very similar to the wild-type operator complex. For G-10 substitutions in hairpin variants that can form bulges at alternative places in the stem, the binding affinity is low and a partly disordered conformation is seen in the electron density maps. The affinity is similar to that of wild-type when the base pairs adjacent to the bulged nucleotide are selected to avoid alternative conformations. Both purines bind in a very similar way in a pocket in the protein. In the C-10 variant, which has very low affinity, the cytidine is partly inserted in the protein pocket rather than intercalated in the RNA stem. Substitution of the wild-type adenosine at position –7 by pyrimidines gives strongly reduced affinities, but the structure of the C-7 complex shows that the base occupies the same position as the A-7 in the wild-type RNA. It is stacked in the RNA and makes no direct contact with the protein. 相似文献
896.
Moulard B Genton P Grid D Jeanpierre M Ouazzani R Mrabet A Morris M LeGuern E Dravet C Mauguière F Utermann B Baldy-Moulinier M Belaidi H Bertran F Biraben A Ali Chérif A Chkili T Crespel A Darcel F Dulac O Geny C Humbert-Claude V Kassiotis P Buresi C Malafosse A 《Human genetics》2002,111(3):255-262
Unverricht-Lundborg disease (ULD) is a progressive myoclonus epilepsy common in Finland and North Africa, and less common in Western Europe. ULD is mostly caused by expansion of a dodecamer repeat in the cystatin B gene ( CSTB) promoter. We performed a haplotype study of ULD chromosomes (ULDc) with the repeat expansion. We included 48 West European Caucasian (WEC) and 47 North African (NA) ULDc. We analysed eight markers flanking CSTB(GT10-D21S1890-D21S1885-D21S2040-D21S1259- CSTB-D21S1912-PFKL-D21S171) and one intragenic variant in the CSTB 3' UTR (A2575G). We observed a founder effect in most of the NA ULD patients, as 61.7% of the NA ULDc (29/47) shared the same haplotype, A1 (1-1-A-1-6-7), for markers D21S1885-D21S2040-A2575G-D21S1259-D21S1912-PFKL. Moreover, if we considered only the markers D21S1885, D21S2040, A2575G and D21S1259, 43 of the 47 NA ULDc shared the same alleles 1-1-A-1, haplotype A. As previously shown, the WEC ULDc were heterogeneous. However, the Baltic haplotype, A3 (5-1-1-A-1-1), was observed in ten WEC ULDc (20.8%) and the CSTB 3'UTR variant, which we called the Alps variant, was observed in 17 ULDc (35.4%). Finally, as almost all NA patients, like Scandinavian patients, were of the haplotype A, we assumed that there was an ancient common founder effect in NA and Baltic ULD patients. We estimated that the putative most recent common ancestral ULD carrier with this haplotype A must have existed about 2,500 years ago (100-150 generations). Finally, this work provides evidence for the existence of only a small number of founder mutations in ULD. 相似文献
897.
Thrombospondin 2 inhibits microvascular endothelial cell proliferation by a caspase-independent mechanism 总被引:5,自引:0,他引:5
下载免费PDF全文
![点击此处可从《Molecular biology of the cell》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Armstrong LC Björkblom B Hankenson KD Siadak AW Stiles CE Bornstein P 《Molecular biology of the cell》2002,13(6):1893-1905
The matricellular protein thrombospondin 2 (TSP2) regulates a variety of cell-matrix interactions. A prominent feature of TSP2-null mice is increased microvascular density, particularly in connective tissues synthesized after injury. We investigated the cellular basis for the regulation of angiogenesis by TSP2 in cultures of murine and human fibroblasts and endothelial cells. Fibroblasts isolated from murine and human dermis synthesize TSP2 mRNA and secrete significant amounts of immunoreactive TSP2, whereas endothelial cells from mouse lung and human dermis did not synthesize TSP2 mRNA or protein. Recombinant mouse TSP2 inhibited growth of human microvascular endothelial cells (HMVECs) mediated by basic fibroblast growth factor, insulin-like growth factor-1, epidermal growth factor, and vascular endothelial growth factor (VEGF). HMVECs exposed to TSP2 in the presence of these growth factors had a decreased proportion of cells in S and G2/M phases. HMVECs cultured with a combination of basic fibroblast growth factor, insulin-like growth factor-1, and epidermal growth factor displayed an increased proportion of nonviable cells in the presence of TSP2, but the addition of VEGF blocked this TSP2-mediated impairment of cell viability. TSP2-mediated inhibition of DNA synthesis by HMVECs in the presence of VEGF was not affected by the broad-spectrum caspase inhibitor zVAD-fmk. Similar findings were obtained with TSP1. Taken together, these observations indicate that either TSP2 or TSP1 can inhibit HMVEC proliferation by inhibition of cell cycle progression and induction of cell death, but the mechanisms responsible for TSP2-mediated inhibition of cell cycle progression are independent from those leading to cell death. 相似文献
898.
HIF-1-induced erythropoietin in the hypoxic retina protects against light-induced retinal degeneration 总被引:40,自引:0,他引:40
Grimm C Wenzel A Groszer M Mayser H Seeliger M Samardzija M Bauer C Gassmann M Remé CE 《Nature medicine》2002,8(7):718-724
Erythropoietin (Epo) is upregulated by hypoxia and provides protection against apoptosis of erythroid progenitors in bone marrow and brain neurons. Here we show in the adult mouse retina that acute hypoxia dose-dependently stimulates expression of Epo, fibroblast growth factor 2 and vascular endothelial growth factor via hypoxia-inducible factor-1alpha (HIF-1alpha) stabilization. Hypoxic preconditioning protects retinal morphology and function against light-induced apoptosis by interfering with caspase-1 activation, a downstream event in the intracellular death cascade. In contrast, induction of activator protein-1, an early event in the light-stressed retina, is not affected by hypoxia. The Epo receptor required for Epo signaling localizes to photoreceptor cells. The protective effect of hypoxic preconditioning is mimicked by systemically applied Epo that crosses the blood retina barrier and prevents apoptosis even when given therapeutically after light insult. Application of Epo may, through the inhibition of apoptosis, be beneficial for the treatment of different forms of retinal disease. 相似文献
899.
900.