全文获取类型
收费全文 | 23015篇 |
免费 | 2073篇 |
国内免费 | 2534篇 |
出版年
2024年 | 34篇 |
2023年 | 190篇 |
2022年 | 310篇 |
2021年 | 879篇 |
2020年 | 762篇 |
2019年 | 897篇 |
2018年 | 859篇 |
2017年 | 710篇 |
2016年 | 847篇 |
2015年 | 1317篇 |
2014年 | 1650篇 |
2013年 | 1829篇 |
2012年 | 2169篇 |
2011年 | 2014篇 |
2010年 | 1335篇 |
2009年 | 1184篇 |
2008年 | 1585篇 |
2007年 | 1343篇 |
2006年 | 1238篇 |
2005年 | 1048篇 |
2004年 | 1034篇 |
2003年 | 949篇 |
2002年 | 862篇 |
2001年 | 413篇 |
2000年 | 313篇 |
1999年 | 261篇 |
1998年 | 230篇 |
1997年 | 146篇 |
1996年 | 134篇 |
1995年 | 138篇 |
1994年 | 102篇 |
1993年 | 88篇 |
1992年 | 88篇 |
1991年 | 78篇 |
1990年 | 64篇 |
1989年 | 67篇 |
1988年 | 54篇 |
1987年 | 46篇 |
1986年 | 40篇 |
1985年 | 39篇 |
1984年 | 26篇 |
1983年 | 21篇 |
1982年 | 31篇 |
1981年 | 18篇 |
1980年 | 13篇 |
1979年 | 28篇 |
1978年 | 15篇 |
1977年 | 12篇 |
1973年 | 10篇 |
1967年 | 9篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
91.
Li-Xin Zhang Hou-Guo Liang Jun Wang Wen-Rui Li Tian-Zhi Yu 《Photosynthesis research》1996,48(3):379-384
The 33 kDa protein of Photosystem II has one intrachain disulfide bond. Fluorescence spectroscopy shows that the major groups in the protein that bind to Ca2+ should be the carboxylic side groups of glutamic acid and/or aspartic acid. Fluorescence and Fourier-transform infrared (FTIR) spectroscopic studies indicate that the conformation of the 33 kDa protein is altered upon reduction, while the reduced protein still retains the secondary structure. FTIR spectroscopy also shows that the metal ions induce a relative decrease of unordered structure and -sheet, and a substantial increase of -helix in both the intact and the reduced 33 kDa protein. This indicates that the addition of cations results in a much more compact structure and that both the intact and the reduced 33 kDa proteins have the ability to bind calcium. The above results may suggest that the disulfide bridge is not essential for calcium binding.Abbreviations CD
circular dichroism
- FTIR
Fourier transform infrared
- La
lanthanum
- PS
photosystem
- Tb
terbium 相似文献
92.
Cytoplasmic chaperones determine the targeting pathway of precursor proteins to mitochondria. 总被引:6,自引:1,他引:5 下载免费PDF全文
Two ATP-dependent cytosolic chaperones, mitochondrial import stimulation factor (MSF) and hsp70, are known to be involved in the import of precursor proteins into mitochondria. Hsp70 generally recognizes unfolded proteins, while MSF specifically recognizes mitochondrial precursor proteins and targets them to mitochondria in a NEM-sensitive manner. Here we analyzed the relative contribution of these chaperones in the import process and confirmed that the precursor proteins are targeted to mitochondria via two distinct pathways: one requiring MSF and the other requiring hsp70. Both pathways depend on distinct proteinaceous components of the outer mitochondrial membrane. The MSF-dependent pathway is NEM-sensitive and requires the hydrolysis of extra-mitochondrial ATP for the release of MSF from the mitochondrial import receptor, whereas the hsp70-dependent pathway is NEM-sensitive and does not require extra-mitochondrial ATP. The NEM-insensitive, hsp70-dependent import became NEM-sensitive depending on the amount of MSF added. The relative importance of the two pathways appears to be determined by the affinities of MSF and hsp70 for the precursor proteins. 相似文献
93.
Binding of nonamer peptides to three HLA-B51 molecules which differ by a single amino acid substitution in the A-pocket 总被引:2,自引:2,他引:0
Akiko Kikuchi Takashi Sakaguchi Kiyoshi Miwa Yuji Takamiya Hans-Georg Rammensee Yutaro Kaneko Masafumi Takiguchi 《Immunogenetics》1996,43(5):268-276
The interaction between 9-mer peptides and HLA-B51 molecules was investigated by quantitative peptide binding assay using
RMA-S cell expressing human β2-microglobulin and HLA-B51 molecules. Of 147 chemically synthesized 9-mer peptides possessing
two anchor residues corresponding to the motif of HLA-B*5101 binding self-peptides, 27 paptides bound to HLA-B*5101 molecules. Pro and Ala at position 2 as well as Ile at position 9 were confirmed to be main anchor residues, while Gly
at position 2 as well as Val, Leu, and Met at position 9 were weak anchor residues for HLA-B*5101. The A-pocket is suspected to have a critical role in peptide binding to MHC class I molecules because this pocket corresponds
to the N-terminus of peptides and has a strong hydrogen bond formed by conserved Tyr residues. Further analysis of peptide
binding to HLA-B*5102 and B*5103 molecules showed that a single amino acid substitution of Tyor for His at residue 171(B*5102) and that of Gly for Trp at residue 167 (B*5103) has a minimum effect in HLA-B51-peptide binding. Since previous studies showed that some HLA-B51 alloreactive CTL clones
failed to kill the cells expressing HLA-B*5102 or HLA-B*5103, these results imply that the structural change of the A-pocket among HLA-B51 subtypes causes a critical conformational
change of the epitope for TCR recognition rather than influences the interaction between peptides and MHC class I molecules. 相似文献
94.
In rodents an intravenous administration of viableCryptococcus (C.) neoformans cells frequently resulted in attachment of intravascular cryptococcal granulomas to inner walls of the large to medium-sized
veins of various organs, including the lungs, liver and spleen. In order to elucidate the pathogenesis of granulomatous changes,
the cells composing the intravascular granulomas were observed by electron microscopic peroxidase (PO) cytochemistry. The
granuloma composing cells could be divided into the following four types according to the pattern of endogenous peroxidase
activity: exudate macrophage (Mφ, type I), PO-negative Mφ (type II), resident Mφ (type III) and other inflammatory cells (type
IV). In the intravenous granulomas of the lung, the percentages of composed cells were 39.0% for type I, 57.9% for type II,
0% for type III and 3.1% for type IV. By contrast, in the interstitial granulomas in the lung, type III Mφs, possibly derived
from alveolar Mφs, played a significant role in granuloma formation. This may indicate that the intravascular granuloma is
almost composed of macrophages derived from monocytes rather than alveolar macrophages. The expression of ICAM-1 on endothelia
of the pulmonary veins was examined by immunoelectron microscopy. An immunogold labeling index was significantly augmented
on the surface of endothelia in response to intravenous challenge ofC. neoformans. The intravascular granuloma demonstrates that the monocytes develop into the granuloma-composing macrophages and suppress
the cryptococcal activities even hi the peripheral blood resulting in an assistance of endothelial functions. 相似文献
95.
Shuji Nakamura David W. Stock Karen L. Wydner Jacques A. Bollekens Kenichi Takeshita Brian M. Nagai Shigeru Chiba Toshio Kitamura Thomas M. Freeland Zhiyong Zhao Jun Minowada Jeanne B. Lawrence Kenneth M. Weiss Frank H. Ruddle 《Genomics》1996,38(3):314
We have cloned a new Dlx gene (Dlx7) from human and mouse that may represent the mammalian orthologue of the newt geneNvHBox-5.The homeodomains of these genes are highly similar to all other vertebrate Dlx genes, and regions of similarity also exist between mammalian Dlx7 and a subset of vertebrate Dlx genes downstream of the homeodomain. The sequence divergence between human and mouse Dlx7 in these regions is greater than that predicted from comparisons of other vertebrate Dlx genes, however, and there is little sequence similarity upstream of the homeodomain both between these two genes and with other Dlx genes. We present evidence for alternative splicing of mouseDlx7upstream of the homeodomain that may account for some of this divergence. We have mapped humanDLX7distal to the 5′ end of the HOXB cluster at an estimated distance of between 1 and 2 Mb by FISH. Both the human and the mouse Dlx7 are shown to be closely linked to Dlx3 in a convergently transcribed orientation. These mapping results support the possibility that vertebrate distal-less genes have been duplicated in concert with the Hox clusters. 相似文献
96.
Kazutoyo Osoegawa Rie Susukida Saishi Okano Jun Kudoh Shinsei Minoshima Nobuyoshi Shimizu Pieter J. de Jong Juergen Groet Jane Ives Hans Lehrach Dean Nizetic Eiichi Soeda 《Genomics》1996,32(3):375
The major phenotypic features of Down syndrome have been correlated with partial trisomies of chromosome 21, allowing us to define the candidate gene region to a 4-Mb segment on the 21q22.2 band. We present here a high-resolution physical map with megabase-sized cosmid/PAC contigs. This ordered clone library has provided unique material for the integration of a variety of mappable objects, including exons, cDNAs, restriction sites, etc. Furthermore, our results have exemplified a strategy for the completion of the chromosome 21 map to sequencing. 相似文献
97.
98.
人分裂细胞核抗原基因片段的筛选、测序及对启动子的分析 总被引:1,自引:0,他引:1
经6.6×105个克隆筛选,从装在λ噬菌体载体Charon30中的人基因库中筛选到了一个含人分裂细胞核抗原(PCNA)基因的克隆。经Southern杂交分析插入基因长约14kb,有较长的5'上游区,但3'端缺少一部分。经亚克隆和测序已确定从5'上游1263bp到3'端与λ载体接点共4969bpPCNA基因片段的核苷酸序列。将PCNA基因启动子核苷酸序列与DNA聚合酶α,拓扑异构酶Ⅱα,胸苷酸激酶基因的启动子进行比较有30%以上同源性,具有“看家基因”特征。在转录起始点的5'上游几百bp的范围内都有与CAT,SP1,E2F,NFHB,Oct1和ATF等转录因子的结合位点相似的核苷酸序列。 相似文献
99.
控制大豆白花亲本籽粒脐色的基因有带R与r之分,带R基因的白花产本与紫花亲本杂交,F1代籽料出现蓝脐性状,其基因型为I-R-W1-tt。当控制脐色的基因有两对相差时(R、r;W1、w1)F2代籽粒脐色分离蓝脐与无色脐之比为9∶7。 相似文献
100.
A novel oncogene, ost, encodes a guanine nucleotide exchange factor that potentially links Rho and Rac signaling pathways. 总被引:19,自引:5,他引:14 下载免费PDF全文
Transfection of NIH3T3 cells with an osteosarcoma expression cDNA library led to the appearance of foci of morphologically transformed cells which were found to harbor a novel oncogene, ost. The ost product was activated by truncation of the N-terminal domain of the ost proto-oncogene and was highly tumorigenic in nude mouse assays. The proto-ost cDNA, isolated subsequently, encodes a predicted protein of 100 kDa containing DH (Db1 homology) and PH (pleckstrin homology) domains. Ost is mainly phosphorylated on serine and localized in the cytoplasm. Purified Ost protein catalyzed guanine nucleotide exchange on RhoA and Cdc42 among the Rho and Ras family members tested, indicating that Ost can activate these small GTP-binding proteins. Ost did not detectably associate with RhoA or Cdc42, but interacted specifically with the GTP-bound form of Rac1, suggesting that Ost can function as an effector of Rac1. These results suggest that Ost is a critical regulatory component which links pathways that signal through Rac1, RhoA and Cdc42. Of the tissues examined, expression of ost was the highest in brain and could be localized to neurons and alpha-tanycytes, suggesting that Ost may participate in axonal transport in these specialized cells. 相似文献