全文获取类型
收费全文 | 706篇 |
免费 | 59篇 |
出版年
2023年 | 3篇 |
2022年 | 11篇 |
2021年 | 16篇 |
2020年 | 11篇 |
2019年 | 14篇 |
2018年 | 23篇 |
2017年 | 14篇 |
2016年 | 17篇 |
2015年 | 42篇 |
2014年 | 34篇 |
2013年 | 57篇 |
2012年 | 57篇 |
2011年 | 51篇 |
2010年 | 35篇 |
2009年 | 32篇 |
2008年 | 30篇 |
2007年 | 38篇 |
2006年 | 36篇 |
2005年 | 33篇 |
2004年 | 27篇 |
2003年 | 25篇 |
2002年 | 25篇 |
2001年 | 7篇 |
2000年 | 3篇 |
1999年 | 3篇 |
1998年 | 7篇 |
1997年 | 5篇 |
1995年 | 10篇 |
1994年 | 7篇 |
1993年 | 6篇 |
1992年 | 10篇 |
1991年 | 9篇 |
1989年 | 5篇 |
1988年 | 5篇 |
1987年 | 3篇 |
1986年 | 3篇 |
1985年 | 2篇 |
1984年 | 3篇 |
1983年 | 3篇 |
1982年 | 4篇 |
1980年 | 3篇 |
1978年 | 2篇 |
1976年 | 2篇 |
1974年 | 5篇 |
1973年 | 4篇 |
1972年 | 5篇 |
1970年 | 2篇 |
1967年 | 3篇 |
1965年 | 2篇 |
1964年 | 2篇 |
排序方式: 共有765条查询结果,搜索用时 93 毫秒
721.
Cristina C. Clement Aniuska Becerra Liusong Yin Valerio Zolla Liling Huang Simone Merlin Antonia Follenzi Scott A. Shaffer Lawrence J. Stern Laura Santambrogio 《The Journal of biological chemistry》2016,291(11):5576-5595
The repertoire of peptides displayed in vivo by MHC II molecules derives from a wide spectrum of proteins produced by different cell types. Although intracellular endosomal processing in dendritic cells and B cells has been characterized for a few antigens, the overall range of processing pathways responsible for generating the MHC II peptidome are currently unclear. To determine the contribution of non-endosomal processing pathways, we eluted and sequenced over 3000 HLA-DR1-bound peptides presented in vivo by dendritic cells. The processing enzymes were identified by reference to a database of experimentally determined cleavage sites and experimentally validated for four epitopes derived from complement 3, collagen II, thymosin β4, and gelsolin. We determined that self-antigens processed by tissue-specific proteases, including complement, matrix metalloproteases, caspases, and granzymes, and carried by lymph, contribute significantly to the MHC II self-peptidome presented by conventional dendritic cells in vivo. Additionally, the presented peptides exhibited a wide spectrum of binding affinity and HLA-DM susceptibility. The results indicate that the HLA-DR1-restricted self-peptidome presented under physiological conditions derives from a variety of processing pathways. Non-endosomal processing enzymes add to the number of epitopes cleaved by cathepsins, altogether generating a wider peptide repertoire. Taken together with HLA-DM-dependent and-independent loading pathways, this ensures that a broad self-peptidome is presented by dendritic cells. This work brings attention to the role of “self-recognition” as a dynamic interaction between dendritic cells and the metabolic/catabolic activities ongoing in every parenchymal organ as part of tissue growth, remodeling, and physiological apoptosis. 相似文献
722.
Giuliana Allegrucci Adalgisa Caccone Donatella Cesaroni Valerio Sbordoni 《Journal of evolutionary biology》1992,5(1):121-148
In this paper we attempt to investigate relationships between the amount of genetic divergence in nuclear genes and the degree of morphological differentiation for different sets of characters in Dolichopoda cave crickets. Six populations representing five Dolichopoda species from Central and Southern Italy have been studied. The overall genetic divergence at nuclear genes was estimated both by single copy DNA-DNA hybridization and allozyme frequencies at 26 loci. Euclidean distances for two multivariate sets of morphometric variables: one describing body and appendage morphology, the other male epiphallus shape. Results showed a close agreement between the branching patterns of ΔTm values from DNA hybridization and Nei's allozyme distance values. On the other hand, patterns of morphological divergence revealed independent trends, although the branching pattern based on epiphallus morphology matched to some extent the phylogenies inferred from molecular data. The relative value of molecular and morphological characters as reliable phylogenetic tracers was evaluated in relation to their dependence on evolutionary factors. Implications of these findings on the calibration of molecular clocks are also discussed. The absolute rate of molecular change based on scDNA was estimated to be at least 0.98% divergence/my/lineage. This result is in agreement with calibrations attempted on other insects. Estimates of time of divergence based on allozymes (Nei's D) were highly consistent with the estimate from geological data. 相似文献
723.
724.
725.
Dr. Shigeji Aoki Shoko Ito-Kuwa Kenjirou Nakamura Valerio Vidotto Kanji Takeo 《Mycoscience》1998,39(3):231-238
Hyphae ofCandida albicans elongated towards the oxygen-rich direction when exposed to gradients of oxygen concentration in thin-layer and capillary-tube
cultures with corn meal (CM) agar. The thin-layer culture was prepared by covering a drop of molten CM agar containingC. albicans cells with a cover slip in Petri dishes. Cells located in the central region of the thin-layered medium neither grew nor
produced hyphae. Cells in the marginal regions at first directed their hyphae in arbitrary directions after forming a small
colony. Hyphae then gradually changed their direction of elongation and eventually oriented towards the nearest margin. Under
anaerobiosis, cells seeded in the thin-layered medium did not grow even in the marginal regions. When exposed to air, the
cells in the marginal regions rapidly began to form hyphae which elongated towards the nearest margin. To prepare an oxygen
gradient in capillary-tube cultures, CM agar, and dilute and dense cell suspensions in CM agar were introduced sequentially
into the capillary tubes, and the end closest to the dense cell suspension was sealed with paraffin. Among cells in the dilute
layer, only that located closest to the meniscus grew well and extended hyphae towards the meniscus, where oxygen concentrations
were highest. These studies suggest a positive aerotropic response in the hyphal growth ofC. albicans. 相似文献
726.
Elisa Molinelli Gabriele Ceccarelli Sonia Fantone Eleonora Di Mercurio Daisy Gambini Andrea Maurizi Jessica Perugini Giovanni Tossetta Valerio Brisigotti Edoardo De Simoni Claudia Sapigni Giulio Rizzetto Anna Campanati Oriana Simonetti Daniela Marzioni Annamaria Offidani 《Pigment cell & melanoma research》2023,36(5):423-430
In the last decades, the concept of adipose organ has emerged, giving adipose tissue an active endocrine and immunologic function through the secretion of multiple cytokines and chemokines that seem to be implicated in the development and progression of several cancer, including cutaneous melanoma. In this pilot experimental study, we analyzed the expression in the peritumor subcutaneous adipose tissue of the most significant adipokines involved in the processes of carcinogenesis and metastasis in a population of melanoma patients and in two control groups composed of melanocytic nevi and epidermoid cysts, respectively. We correlated the results obtained with the main disease prognostic factors observing a statistically significant increase in the expression of PAI1, LEP, CXCL1, NAMPT, and TNF-α at the level of the peritumor tissue of the melanoma samples compared to the control groups and a correlation of the same with the histopathological prognostic factor of melanoma. Our preliminary study shows that the overexpression of PAI1, LEP, CXCL1, NAMPT, and TNF-α may contribute to the growth and to the local aggressiveness of cutaneous melanoma. It opens the hypothesis of a direct oncogenic role of subcutaneous adipose tissue and adipokines in the tumorigenesis of melanoma. 相似文献
727.
Damian Dalcher Jennifer Yihong Tan Cristiana Bersaglieri Rodrigo PeaHernndez Eva Vollenweider Stefan Zeyen Marc W Schmid Valerio Bianchi Stefan Butz Marcin Roganowicz Rostyslav Kuzyakiv Tuncay Baubec Ana Claudia Marques Raffaella Santoro 《The EMBO journal》2020,39(23)
Chromosomes have an intrinsic tendency to segregate into compartments, forming long‐distance contacts between loci of similar chromatin states. How genome compartmentalization is regulated remains elusive. Here, comparison of mouse ground‐state embryonic stem cells (ESCs) characterized by open and active chromatin, and advanced serum ESCs with a more closed and repressed genome, reveals distinct regulation of their genome organization due to differential dependency on BAZ2A/TIP5, a component of the chromatin remodeling complex NoRC. On ESC chromatin, BAZ2A interacts with SNF2H, DNA topoisomerase 2A (TOP2A) and cohesin. BAZ2A associates with chromatin sub‐domains within the active A compartment, which intersect through long‐range contacts. We found that ground‐state chromatin selectively requires BAZ2A to limit the invasion of active domains into repressive compartments. BAZ2A depletion increases chromatin accessibility at B compartments. Furthermore, BAZ2A regulates H3K27me3 genome occupancy in a TOP2A‐dependent manner. Finally, ground‐state ESCs require BAZ2A for growth, differentiation, and correct expression of developmental genes. Our results uncover the propensity of open chromatin domains to invade repressive domains, which is counteracted by chromatin remodeling to establish genome partitioning and preserve cell identity. 相似文献
728.
Zeb1 potentiates genome‐wide gene transcription with Lef1 to promote glioblastoma cell invasion
下载免费PDF全文
![点击此处可从《The EMBO journal》网站下载免费的PDF全文](/ch/ext_images/free.gif)
729.
The question of the possible identity of catalytic and regulatory proton pathways in the chloroplast FoF1 ATPase has been studied using different energy-transfer inhibitors. Venturicidin, a reversible inhibitor of Fo, affects neither the delta mu H(+)-dependent thiol reduction of the membrane-bound chloroplast ATPase nor its ability to be activated by the proton gradient. It seems therefore to block only the proton flow required by the catalytic function of the enzymes. Venturicidin, however, also slows down the deactivation of the thiol-reduced ATPases during uncoupled ATP hydrolysis, following a delta mu H+ activation, but phloridzin, a reversible F1 inhibitor, has the same effect. Tentoxin, an irreversible F1 inhibitor, decreases the rate of ATP hydrolysis but does not affect the rate of deactivation. These findings suggest that catalytic and regulatory H(+)-binding sites are different. No distinction can be made, if any, between protons involved in unmasking the thiol-sensitive groups of F1 and in activating the enzyme. The effect of venturicidin and phloridzin on the deactivation is consistent with an inhibitory effect of newly formed--by ATP hydrolysis--ADP molecules, which might affect the enzyme without passing through the medium. Phosphate at millimolar concentration has an effect similar to low concentrations of phloridzin and venturicidin, probably by a simple back-reaction effect. 相似文献
730.