全文获取类型
收费全文 | 43897篇 |
免费 | 2879篇 |
国内免费 | 16篇 |
出版年
2023年 | 255篇 |
2022年 | 590篇 |
2021年 | 1044篇 |
2020年 | 592篇 |
2019年 | 775篇 |
2018年 | 1063篇 |
2017年 | 889篇 |
2016年 | 1480篇 |
2015年 | 2268篇 |
2014年 | 2437篇 |
2013年 | 3280篇 |
2012年 | 3863篇 |
2011年 | 3681篇 |
2010年 | 2243篇 |
2009年 | 1946篇 |
2008年 | 2717篇 |
2007年 | 2617篇 |
2006年 | 2317篇 |
2005年 | 2119篇 |
2004年 | 2006篇 |
2003年 | 1898篇 |
2002年 | 1718篇 |
2001年 | 359篇 |
2000年 | 236篇 |
1999年 | 339篇 |
1998年 | 436篇 |
1997年 | 290篇 |
1996年 | 292篇 |
1995年 | 255篇 |
1994年 | 268篇 |
1993年 | 242篇 |
1992年 | 166篇 |
1991年 | 173篇 |
1990年 | 171篇 |
1989年 | 140篇 |
1988年 | 115篇 |
1987年 | 114篇 |
1986年 | 87篇 |
1985年 | 112篇 |
1984年 | 120篇 |
1983年 | 83篇 |
1982年 | 97篇 |
1981年 | 98篇 |
1980年 | 97篇 |
1979年 | 84篇 |
1978年 | 50篇 |
1977年 | 65篇 |
1976年 | 44篇 |
1975年 | 48篇 |
1973年 | 52篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
31.
Alba Luengo Zhaoqi Li Dan Y. Gui Lucas B. Sullivan Maria Zagorulya Brian T. Do Raphael Ferreira Adi Naamati Ahmed Ali Caroline A. Lewis Craig J. Thomas Stefani Spranger Nicholas J. Matheson Matthew G. Vander Heiden 《Molecular cell》2021,81(4):691-707.e6
- Download : Download high-res image (172KB)
- Download : Download full-size image
32.
Daneen Schaeffer Filipa Pereira Reis Sean J. Johnson Cec��lia Maria Arraiano Ambro van Hoof 《Nucleic acids research》2012,40(18):9298-9307
The 10-subunit RNA exosome is involved in a large number of diverse RNA processing and degradation events in eukaryotes. These reactions are carried out by the single catalytic subunit, Rrp44p/Dis3p, which is composed of three parts that are conserved throughout eukaryotes. The exosome is named for the 3′ to 5′ exoribonuclease activity provided by a large C-terminal region of the Rrp44p subunit that resembles other exoribonucleases. Rrp44p also contains an endoribonuclease domain. Finally, the very N-terminus of Rrp44p contains three Cys residues (CR3 motif) that are conserved in many eukaryotes but have no known function. These three conserved Cys residues cluster with a previously unrecognized conserved His residue in what resembles a metal-ion-binding site. Genetic and biochemical data show that this CR3 motif affects both endo- and exonuclease activity in vivo and both the nuclear and cytoplasmic exosome, as well as the ability of Rrp44p to associate with the other exosome subunits. These data provide the first direct evidence that the exosome-Rrp44p interaction is functionally important and also provides a molecular explanation for the functional defects when the conserved Cys residues are mutated. 相似文献
33.
34.
Sonia Coni Silvia Maria Serrao Zuleyha Nihan Yurtsever Laura Di Magno Rosa Bordone Camilla Bertani Valerio Licursi Zaira Ianniello Paola Infante Marta Moretti Marialaura Petroni Francesca Guerrieri Alessandro Fatica Alberto Macone Enrico De Smaele Lucia Di Marcotullio Giuseppe Giannini Marella Maroder Enzo Agostinelli Gianluca Canettieri 《Cell death & disease》2020,11(12)
35.
Transthyretin (TTR) protects against A-Beta toxicity by binding the peptide thus inhibiting its aggregation. Previous work showed different TTR mutations interact differently with A-Beta, with increasing affinities correlating with decreasing amyloidogenecity of the TTR mutant; this did not impact on the levels of inhibition of A-Beta aggregation, as assessed by transmission electron microscopy. Our work aimed at probing differences in binding to A-Beta by WT, T119M and L55P TTR using quantitative assays, and at identifying factors affecting this interaction. We addressed the impact of such factors in TTR ability to degrade A-Beta. Using a dot blot approach with the anti-oligomeric antibody A11, we showed that A-Beta formed oligomers transiently, indicating aggregation and fibril formation, whereas in the presence of WT and T119M TTR the oligomers persisted longer, indicative that these variants avoided further aggregation into fibrils. In contrast, L55PTTR was not able to inhibit oligomerization or to prevent evolution to aggregates and fibrils. Furthermore, apoptosis assessment showed WT and T119M TTR were able to protect against A-Beta toxicity. Because the amyloidogenic potential of TTR is inversely correlated with its stability, the use of drugs able to stabilize TTR tetrameric fold could result in increased TTR/A-Beta binding. Here we showed that iododiflunisal, 3-dinitrophenol, resveratrol, [2-(3,5-dichlorophenyl)amino] (DCPA) and [4-(3,5-difluorophenyl)] (DFPB) were able to increase TTR binding to A-Beta; however only DCPA and DFPB improved TTR proteolytic activity. Thyroxine, a TTR ligand, did not influence TTR/A-Beta interaction and A-Beta degradation by TTR, whereas RBP, another TTR ligand, not only obstructed the interaction but also inhibited TTR proteolytic activity. Our results showed differences between WT and T119M TTR, and L55PTTR mutant regarding their interaction with A-Beta and prompt the stability of TTR as a key factor in this interaction, which may be relevant in AD pathogenesis and for the design of therapeutic TTR-based therapies. 相似文献
36.
Evidence has been accumulating to support the process of reinforcement as a potential mechanism in speciation. In many species,
mate choice decisions are influenced by cultural factors, including learned mating preferences (sexual imprinting) or learned
mate attraction signals (e.g., bird song). It has been postulated that learning can have a strong impact on the likelihood
of speciation and perhaps on the process of reinforcement, but no models have explicitly considered learning in a reinforcement
context. We review the evidence that suggests that learning may be involved in speciation and reinforcement, and present a
model of reinforcement via learned preferences. We show that not only can reinforcement occur when preferences are learned
by imprinting, but that such preferences can maintain species differences easily in comparison with both autosomal and sex-linked
genetically inherited preferences. We highlight the need for more explicit study of the connection between the behavioral
process of learning and the evolutionary process of reinforcement in natural systems. 相似文献
37.
Natalia V. Engelhardt Valentina M. Factor Alexander L. Medvinsky Vladimir N. Baranov Maria N. Lazareva Valentina S. Poltoranina 《Differentiation; research in biological diversity》1993,55(1):19-26
Abstract. The A6 antigen - a surface-exposed component shared by mouse oval and biliary epithelial cells - was examined during prenatal development of mouse in order to elucidate its relation to liver progenitor cells. Immunohistochemical demonstration of the antigen was performed at the light and electron microscopy level beginning from the 9.5 day of gestation (26–28 somite pairs).
Up to the 11.5 day of gestation A6 antigen is found only in the visceral endoderm of yolk sac and gut epithelium, while liver diverticulum and liver are A6-negative. In the liver epithelial lineages A6 antigen behaves as a strong and reliable marker of biliary epithelial cells where it is found beginning from their emergence on the 15th day of gestation. It was not revealed in immature hepato-cytes beginning from the 16th day of gestation. However weak expression of the antigen was observed in hepato-blasts on 12–15 days of gestation possibly reflecting their ability to differentiate along either hepatocyte or biliary epithelial cell lineages.
Surprisingly, A6 antigen turned out to be a peculiar marker of the crythroid lineage: in mouse fetuses it distinguished A6 positive liver and spleen erythroblasts from A6 negative early hemopoietic cells of yolk sac origin. Moreover in the liver, A6 antigen probably distinguishes two waves of erythropoiesis: it is found on the erythroblasts from the 11.5 day of gestation onward while first extravascular erythroblasts appear in the liver on the 10th day of gestation. Both fetal and adult erythrocytes are A6-negative.
In the process of organogenesis A6 antigen was revealed in various mouse fetal organs. Usually it was found on plasma membranes of mucosal or ductular epithelial cells. Investigation of A6 antigen's physiological function would probably explain such specific localization. 相似文献
Up to the 11.5 day of gestation A6 antigen is found only in the visceral endoderm of yolk sac and gut epithelium, while liver diverticulum and liver are A6-negative. In the liver epithelial lineages A6 antigen behaves as a strong and reliable marker of biliary epithelial cells where it is found beginning from their emergence on the 15th day of gestation. It was not revealed in immature hepato-cytes beginning from the 16th day of gestation. However weak expression of the antigen was observed in hepato-blasts on 12–15 days of gestation possibly reflecting their ability to differentiate along either hepatocyte or biliary epithelial cell lineages.
Surprisingly, A6 antigen turned out to be a peculiar marker of the crythroid lineage: in mouse fetuses it distinguished A6 positive liver and spleen erythroblasts from A6 negative early hemopoietic cells of yolk sac origin. Moreover in the liver, A6 antigen probably distinguishes two waves of erythropoiesis: it is found on the erythroblasts from the 11.5 day of gestation onward while first extravascular erythroblasts appear in the liver on the 10th day of gestation. Both fetal and adult erythrocytes are A6-negative.
In the process of organogenesis A6 antigen was revealed in various mouse fetal organs. Usually it was found on plasma membranes of mucosal or ductular epithelial cells. Investigation of A6 antigen's physiological function would probably explain such specific localization. 相似文献
38.
Adriana Calderaro Giovanna Piccolo Chiara Gorrini Sara Montecchini Sabina Rossi Maria Cristina Medici Carlo Chezzi Georges Snounou 《PloS one》2012,7(10)
It has been proposed that ovale malaria in humans is caused by two closely related but distinct species of malaria parasites: P. ovale curtisi and P. ovale wallikeri. We have extended and optimized a Real-time PCR assay targeting the parasite’s small subunit ribosomal RNA (ssrRNA) gene to detect both these species. When the assay was applied to 31 archival blood samples from patients diagnosed with P. ovale, it was found that the infection in 20 was due to P. ovale curtisi and in the remaining 11 to P. ovale wallikeri. Thus, this assay provides a useful tool that can be applied to epidemiological investigations of the two newly recognized distinct P. ovale species, that might reveal if these species also differ in their clinical manifestation, drugs susceptibility and relapse periodicity. The results presented confirm that P. ovale wallikeri is not confined to Southeast Asia, since the majority of the patients analyzed in this study had acquired their P. ovale infection in African countries, mostly situated in West Africa. 相似文献
39.
40.
It has long been assumed that serial homologues are ancestrally similar—polysomerism resulting from a “duplication” or “repetition” of forms—and then often diverge—anisomerism, for example, as they become adapted to perform different tasks as is the case with the forelimb and hind limbs of humans. However, such an assumption, with crucial implications for comparative, evolutionary, and developmental biology, and for evolutionary developmental biology, has in general not really been tested by a broad analysis of the available empirical data. Perhaps not surprisingly, more recent anatomical comparisons, as well as molecular knowledge of how, for example, serial appendicular structures are patterned along with different anteroposterior regions of the body axis of bilateral animals, and how “homologous” patterning domains do not necessarily mark “homologous” morphological domains, are putting in question this paradigm. In fact, apart from showing that many so-called “serial homologues” might not be similar at all, recent works have shown that in at least some cases some “serial” structures are indeed more similar to each other in derived taxa than in phylogenetically more ancestral ones, as pointed out by authors such as Owen. In this article, we are taking a step back to question whether such assumptions are actually correct at all, in the first place. In particular, we review other cases of so-called “serial homologues” such as insect wings, arthropod walking appendages, Dipteran thoracic bristles, and the vertebrae, ribs, teeth, myomeres, feathers, and hairs of chordate animals. We show that: (a) there are almost never cases of true ancestral similarity; (b) in evolution, such structures—for example, vertebra—and/or their subparts—for example, “transverse processes”—many times display trends toward less similarity while in many others display trends toward more similarity, that is, one cannot say that there is a clear, overall trend to anisomerism. 相似文献