全文获取类型
收费全文 | 4235篇 |
免费 | 389篇 |
国内免费 | 2篇 |
专业分类
4626篇 |
出版年
2023年 | 14篇 |
2022年 | 43篇 |
2021年 | 82篇 |
2020年 | 59篇 |
2019年 | 69篇 |
2018年 | 95篇 |
2017年 | 81篇 |
2016年 | 133篇 |
2015年 | 201篇 |
2014年 | 196篇 |
2013年 | 339篇 |
2012年 | 340篇 |
2011年 | 323篇 |
2010年 | 219篇 |
2009年 | 181篇 |
2008年 | 272篇 |
2007年 | 284篇 |
2006年 | 260篇 |
2005年 | 242篇 |
2004年 | 189篇 |
2003年 | 201篇 |
2002年 | 220篇 |
2001年 | 53篇 |
2000年 | 37篇 |
1999年 | 56篇 |
1998年 | 54篇 |
1997年 | 23篇 |
1996年 | 34篇 |
1995年 | 26篇 |
1994年 | 29篇 |
1993年 | 23篇 |
1992年 | 25篇 |
1991年 | 13篇 |
1990年 | 20篇 |
1989年 | 18篇 |
1988年 | 17篇 |
1987年 | 12篇 |
1986年 | 16篇 |
1985年 | 7篇 |
1984年 | 11篇 |
1982年 | 9篇 |
1981年 | 9篇 |
1979年 | 7篇 |
1978年 | 8篇 |
1977年 | 13篇 |
1976年 | 6篇 |
1974年 | 11篇 |
1973年 | 7篇 |
1972年 | 9篇 |
1971年 | 9篇 |
排序方式: 共有4626条查询结果,搜索用时 0 毫秒
81.
Simon Nimpf Gregory Charles Nordmann Daniel Kagerbauer Erich Pascal Malkemper Lukas Landler Artemis Papadaki-Anastasopoulou Lyubov Ushakova Andrea Wenninger-Weinzierl Maria Novatchkova Peter Vincent Thomas Lendl Martin Colombini Matthew J. Mason David Anthony Keays 《Current biology : CB》2019,29(23):4052-4059.e4
82.
83.
Sofía Ruiz-Cruz Andrea Erazo Garzon Philip Kelleher Francesca Bottacini Solvej Østergaard Breum Horst Neve Knut J. Heller Finn K. Vogensen Simon Palussière Pascal Courtin Marie-Pierre Chapot-Chartier Evgeny Vinogradov Irina Sadovskaya Jennifer Mahony Douwe van Sinderen 《Microbial biotechnology》2022,15(12):2875-2889
The first step in phage infection is the recognition of, and adsorption to, a receptor located on the host cell surface. This reversible host adsorption step is commonly followed by an irreversible event, which involves phage DNA delivery or release into the bacterial cytoplasm. The molecular components that trigger this latter event are unknown for most phages of Gram-positive bacteria. In the current study, we present a comparative genome analysis of three mutants of Lactococcus cremoris 3107, which are resistant to the P335 group phage TP901-1 due to mutations that affect TP901-1 DNA release. Through genetic complementation and phage infection assays, a predicted lactococcal three-component glycosylation system (TGS) was shown to be required for TP901-1 infection. Major cell wall saccharidic components were analysed, but no differences were found. However, heterologous gene expression experiments indicate that this TGS is involved in the glucosylation of a cell envelope-associated component that triggers TP901-1 DNA release. To date, a saccharide modification has not been implicated in the DNA delivery process of a Gram-positive infecting phage. 相似文献
84.
85.
We report herein the synthesis of new alpha and beta aminooxylated L-fucopyranosyl derivatives for the preparation of glycoclusters through oxime ligation. The glycosylation reaction between activated triacetylated L-fucopyranosyl fluoride and N-hydroxyphthalimide was carried out in the presence of boron trifluoride-diethyl etherate and the stereochemical outcome of glycosylation was compared in dichloromethane, acetonitrile or tetrahydrofuran. Interestingly, an unexpected alpha and beta anomer ratio was obtained in spite of the presence of an acetate participating group at the carbon 2, particularly the 1,2-cis glycosylation was largely favoured in acetonitrile. The resulting alpha and beta N-oxyphthalimido fucopyranosyl derivatives were finally deprotected with methylhydrazine to obtain the corresponding free aminooxylated fucopyranosyls. The structure of single-crystal alpha anomer 12 was analysed by X-ray diffraction. 相似文献
86.
Ribes V Otto DM Dickmann L Schmidt K Schuhbaur B Henderson C Blomhoff R Wolf CR Tickle C Dollé P 《Developmental biology》2007,303(1):66-81
Cytochrome P450 oxidoreductase (POR) acts as an electron donor for all cytochrome P450 enzymes. Knockout mouse Por(-/-) mutants, which are early embryonic (E9.5) lethal, have been found to have overall elevated retinoic acid (RA) levels, leading to the idea that POR early developmental function is mainly linked to the activity of the CYP26 RA-metabolizing enzymes (Otto et al., Mol. Cell. Biol. 23, 6103-6116). By crossing Por mutants with a RA-reporter lacZ transgene, we show that Por(-/-) embryos exhibit both elevated and ectopic RA signaling activity e.g. in cephalic and caudal tissues. Two strategies were used to functionally demonstrate that decreasing retinoid levels can reverse Por(-/-) phenotypic defects, (i) by culturing Por(-/-) embryos in defined serum-free medium, and (ii) by generating compound mutants defective in RA synthesis due to haploinsufficiency of the retinaldehyde dehydrogenase 2 (Raldh2) gene. Both approaches clearly improved the Por(-/-) early phenotype, the latter allowing mutants to be recovered up until E13.5. Abnormal brain patterning, with posteriorization of hindbrain cell fates and defective mid- and forebrain development and vascular defects were rescued in E9.5 Por(-/-) embryos. E13.5 Por(-/-); Raldh2(+/-) embryos exhibited abdominal/caudal and limb defects that strikingly phenocopy those of Cyp26a1(-/-) and Cyp26b1(-/-) mutants, respectively. Por(-/-); Raldh2(+/-) limb buds were truncated and proximalized and the anterior-posterior patterning system was not established. Thus, POR function is indispensable for the proper regulation of RA levels and tissue distribution not only during early embryonic development but also in later morphogenesis and molecular patterning of the brain, abdominal/caudal region and limbs. 相似文献
87.
Halilagic A Ribes V Ghyselinck NB Zile MH Dollé P Studer M 《Developmental biology》2007,303(1):362-375
We have previously shown that retinoic acid (RA) synthesized by the retinaldehyde dehydrogenase 2 (RALDH2) is required in forebrain development. Deficiency in RA due to inactivation of the mouse Raldh2 gene or to complete absence of retinoids in vitamin-A-deficient (VAD) quails, leads to abnormal morphogenesis of various forebrain derivatives. In this study we show that double Raldh2/Raldh3 mouse mutants have a more severe phenotype in the craniofacial region than single null mutants. In particular, the nasal processes are truncated and the eye abnormalities are exacerbated. It has been previously shown that retinoids act mainly on cell proliferation and survival in the ventral forebrain by regulating SHH and FGF8 signaling. Using the VAD quail model, which survives longer than the Raldh-deficient mouse embryos, we found that retinoids act in maintaining the correct position of anterior and dorsal boundaries in the forebrain by modulating FGF8 anteriorly and WNT signaling dorsally. Furthermore, BMP4 and FGF8 signaling are affected in the nasal region and BMP4 is ventrally expanded in the optic vesicle. At the optic cup stage, Pax6, Tbx5 and Bmp4 are ectopically expressed in the presumptive retinal pigmented epithelium (RPE), while Otx2 and Mitf are not induced, leading to a dorsal transdifferentiation of RPE to neural retina. Therefore, besides being required for survival of ventral structures, retinoids are involved in restricting anterior identity in the telencephalon and dorsal identity in the diencephalon and the retina. 相似文献
88.
Neyton S Lespinasse F Lahaye F Staccini P Paquis-Flucklinger V Santucci-Darmanin S 《Experimental cell research》2007,313(17):3680-3693
MSH4 and MSH5 are members of the MutS homolog family, a conserved group of proteins involved in DNA mismatch correction and homologous recombination. Although several studies have provided compelling evidences suggesting that MSH4 and MSH5 could act together in early and late stages of meiotic recombination, their precise roles are poorly understood and recent findings suggest that the human MSH4 protein may also exert a cytoplasmic function. Here we show that MSH4 is present in the cytoplasm and the nucleus of both testicular cells and transfected somatic cells. Confocal studies on transfected cells provide the first evidence that the subcellular localization of MSH4 is regulated, at least in part, by an active nuclear export pathway dependent on the exportin CRM1. We used deletion mapping and mutagenesis to define two functional nuclear export sequences within the C-terminal part of hMSH4 that mediate nuclear export through the CRM1 pathway. Our results suggest that CRM1 is also involved in MSH5 nuclear export. In addition, we demonstrate that dimerization of MSH4 and MSH5 facilitates their nuclear localization suggesting that dimerization may regulate the intracellular trafficking of these proteins. Our findings suggest that nucleocytoplasmic traffic may constitute a regulatory mechanism for MSH4 and MSH5 functions. 相似文献
89.
Uehara M Yashiro K Mamiya S Nishino J Chambon P Dolle P Sakai Y 《Developmental biology》2007,302(2):399-411
The appropriate regulation of retinoic acid signaling is indispensable for patterning of the vertebrate central nervous system along the anteroposterior (A-P) axis. Although both CYP26A1 and CYP26C1, retinoic acid-degrading enzymes that are expressed at the anterior end of the gastrulating mouse embryo, have been thought to play an important role in central nervous system patterning, the detailed mechanism of their contribution has remained largely unknown. We have now analyzed CYP26A1 and CYP26C1 function by generating knockout mice. Loss of CYP26C1 did not appear to affect embryonic development, suggesting that CYP26A1 and CYP26C1 are functionally redundant. In contrast, mice lacking both CYP26A1 and CYP26C1 were found to manifest a pronounced anterior truncation of the brain associated with A-P patterning defects that reflect expansion of posterior identity at the expense of anterior identity. Furthermore, Cyp26a1-/-Cyp26c1-/- mice fail to produce migratory cranial neural crest cells in the forebrain and midbrain. These observations, together with a reevaluation of Cyp26a1 mutant mice, suggest that the activity of CYP26A1 and CYP26C1 is required for correct A-P patterning and production of migratory cranial neural crest cells in the developing mammalian brain. 相似文献
90.