全文获取类型
收费全文 | 178849篇 |
免费 | 10894篇 |
国内免费 | 88篇 |
出版年
2021年 | 1697篇 |
2020年 | 1000篇 |
2019年 | 1275篇 |
2018年 | 2415篇 |
2017年 | 2447篇 |
2016年 | 4937篇 |
2015年 | 9763篇 |
2014年 | 9911篇 |
2013年 | 10471篇 |
2012年 | 11586篇 |
2011年 | 8788篇 |
2010年 | 6340篇 |
2009年 | 6089篇 |
2008年 | 6412篇 |
2007年 | 6419篇 |
2006年 | 6063篇 |
2005年 | 11728篇 |
2004年 | 10324篇 |
2003年 | 8358篇 |
2002年 | 5761篇 |
2001年 | 2148篇 |
2000年 | 1140篇 |
1999年 | 2536篇 |
1998年 | 1664篇 |
1997年 | 1086篇 |
1995年 | 972篇 |
1992年 | 2666篇 |
1991年 | 2634篇 |
1990年 | 2714篇 |
1989年 | 2608篇 |
1988年 | 2520篇 |
1987年 | 2350篇 |
1986年 | 2108篇 |
1985年 | 2309篇 |
1984年 | 1827篇 |
1983年 | 1502篇 |
1982年 | 1219篇 |
1981年 | 1120篇 |
1980年 | 1067篇 |
1979年 | 1508篇 |
1978年 | 1254篇 |
1977年 | 1031篇 |
1976年 | 1063篇 |
1975年 | 1208篇 |
1974年 | 1386篇 |
1973年 | 1382篇 |
1972年 | 1196篇 |
1971年 | 1144篇 |
1970年 | 1021篇 |
1969年 | 1026篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
1.
Suzanne Camus Sergio Menéndez Kenneth Fernandes Nelly Kua Geng Liu Dimitris P. Xirodimas David P. Lane Jean-Christophe Bourdon 《Cell cycle (Georgetown, Tex.)》2012,11(8):1646-1655
The discovery that the single p53 gene encodes several different p53 protein isoforms has initiated a flurry of research into the function and regulation of these novel p53 proteins. Full-length p53 protein level is primarily regulated by the E3-ligase Mdm2, which promotes p53 ubiquitination and degradation. Here, we report that all of the novel p53 isoforms are ubiquitinated and degraded to varying degrees in an Mdm2-dependent and -independent manner, and that high-risk human papillomavirus can degrade some but not all of the novel isoforms, demonstrating that full-length p53 and the p53 isoforms are differentially regulated. In addition, we provide the first evidence that Mdm2 promotes the NEDDylation of p53β. Altogether, our data indicates that Mdm2 can distinguish between the p53 isoforms and modify them differently. 相似文献
2.
E Estébanez-Perpi?á A Bayés J Vendrell M A Jongsma D P Bown J A Gatehouse R Huber W Bode F X Avilés D Reverter 《Journal of molecular biology》2001,313(3):629-638
The cotton bollworm Helicoverpa armigera (Hubner) (Lepidoptera: Noctuidae) is one of the most serious insect pests in Australia, India and China. The larva causes substantial economical losses to legume, fibre, cereal oilseed and vegetable crops. This pest has proven to be difficult to control by conventional means, mainly due to the development of pesticide resistance. We present here the 2.5 A crystal structure from the novel procarboxypeptidase (PCPAHa) found in the gut extracts from H. armigera larvae, the first one reported for an insect. This metalloprotease is synthesized as a zymogen of 46.6 kDa which, upon in vitro activation with Lys-C endoproteinase, yields a pro-segment of 91 residues and an active carboxypeptidase moiety of 318 residues. Both regions show a three-dimensional structure quite similar to the corresponding structures in mammalian digestive carboxypeptidases, the most relevant structural differences being located in the loops between conserved secondary structure elements, including the primary activation site. This activation site contains the motif (Ala)(5)Lys at the C terminus of the helix connecting the pro- and the carboxypeptidase domains. A remarkable feature of PCPAHa is the occurrence of the same (Ala)(6)Lys near the C terminus of the active enzyme. The presence of Ser255 in PCPAHa instead of Ile and Asp found in the pancreatic A and B forms, respectively, enlarges the S1' specificity pocket and influences the substrate preferences of the enzyme. The C-terminal tail of the leech carboxypeptidase inhibitor has been modelled into the PCPAHa active site to explore the substrate preferences and the enzymatic mechanism of this enzyme. 相似文献
3.
The phylogeny of the fungus gnat family Mycetophilidae (Diptera) is reconstructed with a focus on the species‐rich and taxonomically difficult subfamilies Gnoristinae and Mycomyinae. The multigene phylogenetic analyses are based on five nuclear (18S, 28S, CAD, MCS, ITS2) and four mitochondrial (12S, 16S, COI, CytB) gene markers. The analyses strongly support the monophyly of Mycetophilidae and the subfamilies Manotinae, Sciophilinae, Leiinae, and Mycomyinae, although Gnoristinae is paraphyletic with respect to Mycetophilinae. All the genera and groups of genera included are supported as monophyletic, except for Acomoptera Vockeroth, Boletina Staeger, Dziedzickia Johannsen, Ectrepesthoneura Enderlein, and Neoempheria Osten Sacken. Ancestral character state reconstructions were applied to two morphological features present in Gnoristinae and Mycomyinae (i.e. presence of setae on wing membrane and wing vein R4) in order to assess their evolution. The wing vein R4 appears as an unstable character, spread throughout different clades. A dated phylogeny of the family Mycetophilidae showed that most of the subfamilies of Mycetophilidae originated and diversified during the Cretaceous. The youngest subfamilies, originated in the Paleogene, appear to be Mycomyinae and Mycetophilinae. 相似文献
4.
Elevated levels of intracellular calcium are a major cause of myocardial dysfunction. To find possible mediators of the deregulated calcium we searched for EF-hand calcium-binding proteins of the S100 family. By PCR technology we identified three members of the S100 protein family (S100 alpha, CACY, and CAPL) in the human heart. We cloned the corresponding cDNAs and examined their expression levels in various human tissues by Northern blot analysis. All three proteins are expressed at high levels in the human heart. Whereas CACY and CAPL mRNAs are expressed ubiquitously, S100 alpha mRNA is restricted to heart, skeletal muscle, and brain. Interestingly, the expression pattern of S100 alpha, CACY, and CAPL in human tissues differs significantly from that in rodent tissues. 相似文献
5.
6.
7.
8.
Wendy A. Douglass Robert H. Hyland Christopher D. Buckley Aymen Al-Shamkhani Jacqueline M. Shaw Sarah L. Scarth David L. Simmons S.K.Alex Law 《FEBS letters》1998,440(3):125
The cysteine-rich region (CRR) of the β2 integrin subunit was replaced by that of β1 to give the chimera β2NV1. β2NV1 can combine with αL to form a variant leukocyte-function-associated antigen (LFA)-1 on COS cell surface, suggesting that the specificity of the β2 interaction with αL does not lie in the CRR. Unlike those expressing wild-type LFA-1, COS cells expressing αLβ2NV1 are constitutively active in intercellular adhesion molecule (ICAM)-1 adhesion. These results suggest that activation of LFA-1 involves the release of an intramolecular constraint, which is maintained, in part, by the authentic β2 CRR. 相似文献
9.
A putative GDP–GTP exchange factor is required for development of the excretory cell in Caenorhabditis elegans
下载免费PDF全文
![点击此处可从《EMBO reports》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Norio Suzuki Matthew Buechner Kiyoji Nishiwaki David H. Hall Hiroyuki Nakanishi Yoshimi Takai Naoki Hisamoto Kunihiro Matsumoto 《EMBO reports》2001,2(6):530-535
The Caenorhabditis elegans excretory cell extends tubular processes, called canals, along the basolateral surface of the epidermis. Mutations in the exc-5 gene cause tubulocystic defects in this canal. Ultrastructural analysis suggests that exc-5 is required for the proper placement of cytoskeletal elements at the apical epithelial surface. exc-5 encodes a protein homologous to guanine nucleotide exchange factors and contains motif architecture similar to that of FGD1, which is responsible for faciogenital dysplasia. exc-5 interacts genetically with mig-2, which encodes Rho GTPase. These results suggest that EXC-5 controls the structural organization of the excretory canal by regulating Rho family GTPase activities. 相似文献
10.