全文获取类型
收费全文 | 1615篇 |
免费 | 121篇 |
国内免费 | 2篇 |
专业分类
1738篇 |
出版年
2023年 | 7篇 |
2022年 | 26篇 |
2021年 | 29篇 |
2020年 | 20篇 |
2019年 | 23篇 |
2018年 | 42篇 |
2017年 | 36篇 |
2016年 | 51篇 |
2015年 | 82篇 |
2014年 | 88篇 |
2013年 | 113篇 |
2012年 | 124篇 |
2011年 | 111篇 |
2010年 | 84篇 |
2009年 | 78篇 |
2008年 | 98篇 |
2007年 | 103篇 |
2006年 | 102篇 |
2005年 | 82篇 |
2004年 | 76篇 |
2003年 | 63篇 |
2002年 | 59篇 |
2001年 | 17篇 |
2000年 | 11篇 |
1999年 | 16篇 |
1998年 | 20篇 |
1997年 | 14篇 |
1996年 | 11篇 |
1995年 | 8篇 |
1994年 | 12篇 |
1993年 | 14篇 |
1992年 | 13篇 |
1991年 | 17篇 |
1990年 | 9篇 |
1989年 | 5篇 |
1988年 | 4篇 |
1987年 | 6篇 |
1986年 | 3篇 |
1985年 | 3篇 |
1984年 | 11篇 |
1983年 | 4篇 |
1982年 | 6篇 |
1981年 | 4篇 |
1979年 | 3篇 |
1978年 | 6篇 |
1976年 | 2篇 |
1975年 | 5篇 |
1974年 | 3篇 |
1972年 | 4篇 |
1968年 | 2篇 |
排序方式: 共有1738条查询结果,搜索用时 0 毫秒
101.
We compared morphometric parameters of the contours of cells in four pairs of non-transformed mouse and rat lines and of the same lines transformed by oncogenes of the RAS family. As expected, the mean areas of all RAS-transformed lines were much smaller than those of their non-transformed counterparts. At the same time the average length of cell projection did not regularly decrease after transformation. These results show that transformation induced by expression of RAS oncogene selectively affect only one component of spreading, namely transversal spreading and not longitudinal spreading; these changes result in an increase of antero-posterior polarity of transformed fibroblasts. 相似文献
102.
Herrera-Vigenor F Hernández-García R Valadez-Sánchez M Vázquez-Prado J Reyes-Cruz G 《Biochemical and biophysical research communications》2006,347(4):924-930
Calcium-sensing receptor (CaR) activates intracellular pathways controlling calcium homeostasis. CaR carboxyl-terminal mutants associated with metabolic diseases suggest that unidentified proteins interact with the carboxyl-terminal region of this receptor. To address this possibility, we screened for CaR-interacting proteins using the carboxyl terminus of CaR (CaRDelta895-1075 deletion mutant). We identified AMSH, an ubiquitin isopeptidase, as a CaR-interacting partner. AMSH caused a decrease on the signaling properties of wild-type and mutant CaR. Our results indicate that AMSH, which has been recently characterized as a regulator of the endosomal sorting of epidermal growth factor receptor, represents a novel modulator of CaR signaling. 相似文献
103.
To our knowledge there has been no study of the effect of everyday air pollution on olfactory function. It was therefore the aim of this study to compare the olfactory performance of long-term residents of Mexico City, an environment with high air pollution, with the olfactory performance of residents of the Mexican state of Tlaxcala, a region geographically similar to Mexico City but with low air pollution. Healthy volunteers [82 Mexico City subjects (MEX), 86 Tlaxcala subjects (TLX)] 20-63 years of age and balanced for age and gender between the two localities were tested for the perception of the odors of everyday beverages presented in squeeze bottles. When tested with ascending concentrations of stimuli in a three-way oddball paradigm, residents of Tlaxcala detected the odors of instant coffee and of an orange drink at significantly lower concentrations than residents of Mexico City. They also performed significantly better in discriminating between the two similar-smelling Mexican beverages horchata and atole in an oddball test. Significant differences between the two populations in overall olfactory performance were apparent in three of the four age classes (20- to 29-, 30- to 39-, and 40- to 49-year-old subjects) but not in the 50-63 years age class. About 10% of MEX subjects compared to about 2% of TLX subjects were judged to have poor olfactory function; all were from the older age classes (mean age: 48.6 years). Thus, air pollution in Mexico City appears to have a substantial impact on olfactory function even in young and middle-aged residents. 相似文献
104.
Stessin AM Zippin JH Kamenetsky M Hess KC Buck J Levin LR 《The Journal of biological chemistry》2006,281(25):17253-17258
Nerve growth factor (NGF) and the ubiquitous second messenger cyclic AMP (cAMP) are both implicated in neuronal differentiation. Multiple studies indicate that NGF signals to at least a subset of its targets via cAMP, but the link between NGF and cAMP has remained elusive. Here, we have described the use of small molecule inhibitors to differentiate between the two known sources of cAMP in mammalian cells, bicarbonate- and calcium-responsive soluble adenylyl cyclase (sAC) and G protein-regulated transmembrane adenylyl cyclases. These inhibitors, along with sAC-specific small interfering RNA, reveal that sAC is uniquely responsible for the NGF-elicited rise in cAMP and is essential for the NGF-induced activation of the small G protein Rap1 in PC12 cells. In contrast and as expected, transmembrane adenylyl cyclase-generated cAMP is responsible for Rap1 activation by the G protein-coupled receptor ligand PACAP (pituitary adenylyl cyclase-activating peptide). These results identify sAC as a mediator of NGF signaling and reveal the existence of distinct pathways leading to cAMP-dependent signal transduction. 相似文献
105.
Autosomal recessive ichthyosis with hypotrichosis caused by a mutation in ST14, encoding type II transmembrane serine protease matriptase 下载免费PDF全文
Basel-Vanagaite L Attia R Ishida-Yamamoto A Rainshtein L Ben Amitai D Lurie R Pasmanik-Chor M Indelman M Zvulunov A Saban S Magal N Sprecher E Shohat M 《American journal of human genetics》2007,80(3):467-477
In this article, we describe a novel autosomal recessive ichthyosis with hypotrichosis syndrome, characterized by congenital ichthyosis associated with abnormal hair. Using homozygosity mapping, we mapped the disease locus to 11q24.3-q25. We screened the ST14 gene, which encodes matriptase, since transplantation of skin from matriptase(-/-)-knockout mice onto adult athymic nude mice has been shown elsewhere to result in an ichthyosislike phenotype associated with almost complete absence of erupted pelage hairs. Mutation analysis revealed a missense mutation, G827R, in the highly conserved peptidase S1-S6 domain. Marked skin hyperkeratosis due to impaired degradation of the stratum corneum corneodesmosomes was observed in the affected individuals, which suggests that matriptase plays a significant role in epidermal desquamation. 相似文献
106.
AJ Pérez-Berná A Ortega-Esteban R Menéndez-Conejero DC Winkler M Menéndez AC Steven SJ Flint PJ de Pablo C San Martín 《The Journal of biological chemistry》2012,287(37):31582-31595
Adenovirus assembly concludes with proteolytic processing of several capsid and core proteins. Immature virions containing precursor proteins lack infectivity because they cannot properly uncoat, becoming trapped in early endosomes. Structural studies have shown that precursors increase the network of interactions maintaining virion integrity. Using different biophysical techniques to analyze capsid disruption in vitro, we show that immature virions are more stable than the mature ones under a variety of stress conditions and that maturation primes adenovirus for highly cooperative DNA release. Cryoelectron tomography reveals that under mildly acidic conditions mimicking the early endosome, mature virions release pentons and peripheral core contents. At higher stress levels, both mature and immature capsids crack open. The virus core is completely released from cracked capsids in mature virions, but it remains connected to shell fragments in the immature particle. The extra stability of immature adenovirus does not equate with greater rigidity, because in nanoindentation assays immature virions exhibit greater elasticity than the mature particles. Our results have implications for the role of proteolytic maturation in adenovirus assembly and uncoating. Precursor proteins favor assembly by establishing stable interactions with the appropriate curvature and preventing premature ejection of contents by tightly sealing the capsid vertices. Upon maturation, core organization is looser, particularly at the periphery, and interactions preserving capsid curvature are weakened. The capsid becomes brittle, and pentons are more easily released. Based on these results, we hypothesize that changes in core compaction during maturation may increase capsid internal pressure to trigger proper uncoating of adenovirus. 相似文献
107.
108.
29 DNA polymerase achieves a functional coupling between its 3′–5′ exonuclease and polymerization activities by means of important contacts with the DNA at both active sites. The placement and orientation of residues Lys538, Lys555, Lys557, Gln560, Thr571, Thr573 and Lys575 in a modelled 29 DNA polymerase–DNA complex suggest a DNA-binding role. In addition, crystal structure of 29 DNA polymerase–oligo (dT)5 complex showed Leu567, placed at the tip of the thumb subdomain, lying between the two 3′-terminal bases at the exonuclease site. Single replacement of these 29 DNA polymerase residues by alanine was made, and mutant derivatives were overproduced and purified to homogeneity. The results obtained in the assay of their synthetic and degradative activities, as well as their coordination, allow us to propose: (1) a primer-terminus stabilization role at the polymerase active site for residues Lys538, Thr573 and Lys575, (2) a primer-terminus stabilization role at the exonuclease active site for residues Leu567 and Lys555 and (3) a primer-terminus binding role in both editing and polymerization modes for residue Gln560. The results presented here lead us to propose 29 DNA polymerase thumb as the main subdomain responsible for the coordination of polymerization and exonuclease activities. 相似文献
109.
Vallejos-Almirall Alejandro Riquelme Margarita Uribe Elena Agurto-Muñoz Cristian Rosas Anali Vergara Carola 《Journal of applied phycology》2022,34(5):2371-2382
Journal of Applied Phycology - Ultraviolet (UV) radiation generates cyclobutane pyrimidine dimer (CPD) photoproducts in the DNA of skin cells, causing photoaging and non-melanoma skin cancer.... 相似文献
110.
Uracil-DNA glycosylase (UDG) is an enzyme involved in the base excision repair pathway. It specifically removes uracil from both single-stranded and double-stranded DNA. The genome of the Bacillus subtilis phage 29 is a linear double-stranded DNA with a terminal protein covalently linked at each 5'-end. Replication of 29 DNA starts by a protein-priming mechanism and generates intermediates that have long stretches of single-stranded DNA. By using in vivo chemical cross-linking and affinity chromatography techniques, we found that UDG is a cellular target for the early viral protein p56. Addition of purified protein p56 to B. subtilis extracts inhibited the endogenous UDG activity. Moreover, extracts from 29-infected cells were deficient in UDG activity. We suggested that inhibition of the cellular UDG is a defense mechanism developed by 29 to prevent the action of the base excision repair pathway if uracil residues arise in their replicative intermediates. Protein p56 is the first example of a UDG inhibitor encoded by a non-uracil-containing viral DNA. 相似文献