全文获取类型
收费全文 | 6452篇 |
免费 | 403篇 |
国内免费 | 1篇 |
出版年
2023年 | 22篇 |
2022年 | 33篇 |
2021年 | 89篇 |
2020年 | 76篇 |
2019年 | 84篇 |
2018年 | 131篇 |
2017年 | 101篇 |
2016年 | 180篇 |
2015年 | 265篇 |
2014年 | 350篇 |
2013年 | 497篇 |
2012年 | 561篇 |
2011年 | 496篇 |
2010年 | 327篇 |
2009年 | 280篇 |
2008年 | 427篇 |
2007年 | 371篇 |
2006年 | 368篇 |
2005年 | 325篇 |
2004年 | 337篇 |
2003年 | 338篇 |
2002年 | 314篇 |
2001年 | 62篇 |
2000年 | 59篇 |
1999年 | 61篇 |
1998年 | 65篇 |
1997年 | 60篇 |
1996年 | 56篇 |
1995年 | 45篇 |
1994年 | 61篇 |
1993年 | 41篇 |
1992年 | 41篇 |
1991年 | 28篇 |
1990年 | 23篇 |
1989年 | 19篇 |
1988年 | 19篇 |
1987年 | 15篇 |
1986年 | 11篇 |
1985年 | 16篇 |
1984年 | 15篇 |
1983年 | 22篇 |
1982年 | 15篇 |
1981年 | 26篇 |
1980年 | 23篇 |
1979年 | 13篇 |
1978年 | 6篇 |
1977年 | 17篇 |
1976年 | 6篇 |
1975年 | 7篇 |
1974年 | 9篇 |
排序方式: 共有6856条查询结果,搜索用时 78 毫秒
951.
952.
Corrado Occella Dario Bleidl Paolo Nozza Samantha Mascelli Alessandro Raso Giorgio Gimelli Stefania Gimelli Elisa Tassano 《PloS one》2013,8(4)
Porokeratosis is a rare disease of epidermal keratinization characterized by the histopathological feature of the cornoid lamella, a column of tightly fitted parakeratocytic cells, whose etiology is still unclear. Porokeratosis of Mibelli is a subtype of porokeratosis presenting a single plaque or a small number of plaques of variable size located unilaterally on limbs. It frequently appears in childhood and occurs with a higher incidence in males. Cytogenetic analyses were performed in all members of the family on lesioned and uninvolved skin. An array-CGH analysis was also performed utilizing the Human Genome CGH Microarray Kit G3 400 with 5.3 KB overall median probe spacing. Gene expression was performed on skin fibroblasts. In this study, we describe a Caucasian healthy 4-year-old child and his father showing features of porokeratosis of Mibelli. Array-CGH analysis revealed an interstitial 429.5 Kb duplication of chromosome 18p11.32-p11.3 containing four genes, namely: SMCHD1, EMILIN2, LPIN2, and MYOM1 both in patient and his father. EMILIN2 resulted overexpressed on skin fibroblasts. Also other members of this family, without evident signs of porokeratosis, carried the same duplication. Among these genes, we focused our attention on elastin microfibril interfacer 2 (EMILIN2) gene. Apoptosis plays a fundamental role in maintaining epidermal homeostasis, balancing keratinocytes proliferation, and forming the stratum corneum. EMILIN2 is known to trigger the apoptosis of different cell lines negatively affecting cell survival. It is expressed in the skin. We could speculate that the duplication and overexpression of EMILIN2 cause an abnormal apoptosis of epidermal keratinocytes and alter the process of keratinization, even if other epigenetic and genetic factors could also be involved. Our results could contribute to a better understanding of the pathogenesis of porokeratosis of Mibelli. 相似文献
953.
Patrycja Ledwoń Fosca Errante Anna Maria Papini Paolo Rovero Rafal Latajka 《化学与生物多样性》2021,18(2):e2000833
Cosmeceutical field, which merges cosmetics and pharmaceuticals, is nowadays a highly investigated research area, because a scientific demonstration of the claimed bioactivity of new cosmeceutical ingredients is increasingly requested. In fact, an aspect differentiating traditional cosmetics from cosmeceuticals is the identification and characterization of the active ingredients and demonstrating its efficacy in the claimed activity. An interesting group of bioactive cosmeceutical ingredients are peptides, which due to their particular properties, meets most of the requirements presented by the cosmeceutical industry when composing new formulas. In this context, beside bioactivity, two additional aspects have been recently considered, when dealing with peptides as cosmeceutical ingredients: bioavailability and stability. We describe herein novel methods applied in order to enhance peptides skin-penetration and stability, reviewing both scientific articles and patents, issued in the cosmeceutical arena. 相似文献
954.
955.
956.
The genus Primeuchroeus Linsenmaier, 1968 from China is revised and an illustrated identification key is produced for the first time. Three species are recorded from China, with one species, Primeuchroeus yongdaerianus Kim, new to China. 相似文献
957.
Pelosi Paolo; Pisanelli Anna Maria; Baldaccini Natale Emilio; Gagliardo Anna 《Chemical senses》1981,6(2):77-85
The odorant 2-isobutyl-3-methoxypyrazine binds to cow olfactorymucosa homogenate. The complex, which can be separated by gelfiltration on Sephadex G-100, appears to be made up of fourmacromolecular species. No significant binding has been measuredwith respiratory epithelium. The binding disappears after treatmentwith proteolytic enzymes, or in a SDS containing buffer, thusindicating that the receptors are proteins. Complete loss ofbinding capacity has been also observed as a consequence ofdialysis: this suggests the involvement of a low molecular weightcomponent. 相似文献
958.
959.
Valentina Diehl Martin Wegner Paolo Grumati Koraljka Husnjak Simone Schaubeck Andrea Gubas Varun
Jayeshkumar Shah Ibrahim
H Polat Felix Langschied Cristian Prieto-Garcia Konstantin Müller Alkmini Kalousi Ingo Ebersberger Christian
H Brandts Ivan Dikic Manuel Kaulich 《Nucleic acids research》2021,49(10):5684
Combinatorial CRISPR-Cas screens have advanced the mapping of genetic interactions, but their experimental scale limits the number of targetable gene combinations. Here, we describe 3Cs multiplexing, a rapid and scalable method to generate highly diverse and uniformly distributed combinatorial CRISPR libraries. We demonstrate that the library distribution skew is the critical determinant of its required screening coverage. By circumventing iterative cloning of PCR-amplified oligonucleotides, 3Cs multiplexing facilitates the generation of combinatorial CRISPR libraries with low distribution skews. We show that combinatorial 3Cs libraries can be screened with minimal coverages, reducing associated efforts and costs at least 10-fold. We apply a 3Cs multiplexing library targeting 12,736 autophagy gene combinations with 247,032 paired gRNAs in viability and reporter-based enrichment screens. In the viability screen, we identify, among others, the synthetic lethal WDR45B-PIK3R4 and the proliferation-enhancing ATG7-KEAP1 genetic interactions. In the reporter-based screen, we identify over 1,570 essential genetic interactions for autophagy flux, including interactions among paralogous genes, namely ATG2A-ATG2B, GABARAP-MAP1LC3B and GABARAP-GABARAPL2. However, we only observe few genetic interactions within paralogous gene families of more than two members, indicating functional compensation between them. This work establishes 3Cs multiplexing as a platform for genetic interaction screens at scale. 相似文献
960.
Massimo Coletta Paolo Ascenzi Laura Bravin Gino Amiconi Martino Bolognesi Mario Guarneri 《Journal of biomolecular structure & dynamics》2013,31(4):959-972
Abstract The effect of activating dipeptides, sequentially homologous to the Ile 16-Val 17 N-terminus of bovine β-trypsin (β-trypsin), on equilibria involved in the binding of strong ligands (i.e., n-butylamine, the bovine basic pancreatic trypsin inhibitor (Kunitz-type inhibitor; BPTI) and the porcine pancreatic secretory trypsin inhibitor (Kazal-type inhibitor, type I; PSTI)) to bovine trypsinogen (trypsinogen) was investigated at pH 5.5 (I = 0.1 M) and T = 21.0 ± 0.5°C; under the same experimental conditions, thermodynamics for the binding of strong ligands to β-trypsin was also obtained. The equilibria involved in the binding of activating dipeptides and/or inhibitors to β-trypsin and to its zymogen are described according to an induced-fit formalism, taking into account ligand-linked interaction(s) between different functional and structural domains of the (pro)enzyme possibly involved in the trypsinogen-to-β-trypsin activation pathway. The analysis of data is focussed on parameters describing interactions between the so-called Ile-Val pocket (where the Ile16-Val17/V-terminus of β-trypsin or activating dipeptides bind) and the primary and/or secondary recognition subsite(s) (where strong ligands associate) present in the (pro)enzyme. Such an analysis allows to dissect the contributions due to the primary recognition subsite, where small mono-functional ligands (e.g., n-butylamine) bind, from those of the secondary subsite(s), which are additional recognition clefts for macromolecular inhibitors (e.g., BPTI and PSTI). 相似文献