全文获取类型
收费全文 | 1232篇 |
免费 | 55篇 |
国内免费 | 68篇 |
出版年
2023年 | 4篇 |
2022年 | 11篇 |
2021年 | 16篇 |
2020年 | 13篇 |
2019年 | 18篇 |
2018年 | 19篇 |
2017年 | 19篇 |
2016年 | 26篇 |
2015年 | 30篇 |
2014年 | 35篇 |
2013年 | 87篇 |
2012年 | 27篇 |
2011年 | 52篇 |
2010年 | 34篇 |
2009年 | 53篇 |
2008年 | 53篇 |
2007年 | 64篇 |
2006年 | 56篇 |
2005年 | 57篇 |
2004年 | 52篇 |
2003年 | 69篇 |
2002年 | 33篇 |
2001年 | 40篇 |
2000年 | 26篇 |
1999年 | 32篇 |
1998年 | 30篇 |
1997年 | 39篇 |
1996年 | 34篇 |
1995年 | 49篇 |
1994年 | 46篇 |
1993年 | 21篇 |
1992年 | 23篇 |
1991年 | 19篇 |
1990年 | 13篇 |
1989年 | 11篇 |
1988年 | 23篇 |
1987年 | 15篇 |
1986年 | 14篇 |
1985年 | 20篇 |
1984年 | 12篇 |
1983年 | 10篇 |
1982年 | 16篇 |
1981年 | 8篇 |
1980年 | 12篇 |
1979年 | 3篇 |
1978年 | 7篇 |
1977年 | 3篇 |
1976年 | 1篇 |
排序方式: 共有1355条查询结果,搜索用时 62 毫秒
271.
稻胚凝集素(RGL)在开花后7—13天之间合成活性很强,15天以后明显下降。7—13天之间RGL合成相当旺盛是由于这一时期编码RGL的mRNA得到迅速转录,而在开花后15—30天之间以及萌发4小时内RGL的合成主要是由胚分化发育期间(7—13天)所形成的mRNA所指导的。RGL主要在水稻胚胎发育过程中合成、积累,在萌发过程中几乎不表达,所以RGL是胚胎特异的蛋白质。 相似文献
272.
Khaddouj Benmoussa Johan Garaude Rebeca Acín-Pérez 《Journal of molecular biology》2018,430(21):3906-3921
Metabolic reprogramming of cells from the innate immune system is one of the most noteworthy topics in immunological research nowadays. Upon infection or tissue damage, innate immune cells, such as macrophages, mobilize various immune and metabolic signals to mount a response best suited to eradicate the threat. Current data indicate that both the immune and metabolic responses are closely interconnected. On account of its peculiar position in regulating both of these processes, the mitochondrion has emerged as a critical organelle that orchestrates the coordinated metabolic and immune adaptations in macrophages. Significant effort is now underway to understand how metabolic features of differentiated macrophages regulate their immune specificities with the eventual goal to manipulate cellular metabolism to control immunity. In this review, we highlight some of the recent work that place cellular and mitochondrial metabolism in a central position in the macrophage differentiation program. 相似文献
273.
Improving the recombinant human erythropoietin glycosylation using microsome supplementation in CHO cell‐free system
下载免费PDF全文
![点击此处可从《Biotechnology and bioengineering》网站下载免费的PDF全文](/ch/ext_images/free.gif)
274.
Fumi Ota Tetsuya Hirayama Yasuhiko Kizuka Yoshiki Yamaguchi Reiko Fujinawa Masahiro Nagata Hendra S. Ismanto Bernd Lepenies Jonas Aretz Christoph Rademacher Peter H. Seeberger Takashi Angata Shinobu Kitazume Keiichi Yoshida Tomoko Betsuyaku Kozui Kida Sho Yamasaki Naoyuki Taniguchi 《Biochimica et Biophysica Acta (BBA)/General Subjects》2018,1862(7):1592-1601
Background
Langerin, a C-type lectin receptor (CLR) expressed in a subset of dendritic cells (DCs), binds to glycan ligands for pathogen capture and clearance. Previous studies revealed that langerin has an unusual binding affinity toward 6-sulfated galactose (Gal), a structure primarily found in keratan sulfate (KS). However, details and biological outcomes of this interaction have not been characterized. Based on a recent discovery that the disaccharide L4, a KS component that contains 6-sulfo-Gal, exhibits anti-inflammatory activity in mouse lung, we hypothesized that L4-related compounds are useful tools for characterizing the langerin-ligand interactions and their therapeutic application.Methods
We performed binding analysis between purified long and short forms of langerin and a series of KS disaccharide components. We also chemically synthesized oligomeric derivatives of L4 to develop a new high-affinity ligand of langerin.Results
We show that the binding critically requires the 6-sulfation of Gal and that the long form of langerin displays higher affinity than the short form. The synthesized trimeric (also designated as triangle or Tri) and polymeric (pendant) L4 derivatives displayed over 1000-fold higher affinity toward langerin than monomeric L4. The pendant L4, but not the L4 monomer, was found to effectively transduce langerin signaling in a model cell system.Conclusions
L4 is a specific ligand for langerin. Oligomerization of L4 unit increased the affinity toward langerin.General significance
These results suggest that oligomeric L4 derivatives will be useful for clarifying the langerin functions and for the development of new glycan-based anti-inflammatory drugs. 相似文献275.
Activity of natural toxins against the silverleaf whitefly, Bemisia argentifolii, using a novel feeding bioassay system 总被引:1,自引:0,他引:1
Elizabeth W. Davidson Rufino B. R. Patron Lawrence A. Lacey Roger Frutos Alain Vey Donald L. Hendrix 《Entomologia Experimentalis et Applicata》1996,79(1):25-32
An assay system was developed for the adult silverleaf whitefly, Bemisia argentifolii Bellows & Perring (Homoptera: Aleyrodidae). This practical device was constructed from standard disposable laboratory materials. Whiteflies were harvested directly from the leaf and into a collection vial by vacuum aspiration, minimizing physical damage to the insect. Insects were fed through a cellulose mixed-ester membrane on a diet of 20–27% sucrose alone or sucrose in an extract of zucchini (Curcurbita moschata Duchense). Mortality and honeydew production were scored. At 22–25°C and 50–55% relative humidity, control mortality generally remained at or below 15% during a 48 h assay period. The bioassay system was first tested using the insecticide, Imidacloprid, then used to screen a number of natural products with potential insecticidal activity against the whitefly. Destruxins extracted from the entomopathogenic fungus, Metarhizium anisopliae, and the natural insecticide/nematicide, Ivermectin, as well as bee venom and two of its components, melittin and phospholipase A2, were found to be toxic to B. argentifolii. Five lectins, Bacillus thuringiensis toxins, gossypol, an extract of Paeciliomyces fumosoroseus, wasp and scorpion venom, and a trypsin inhibitor were not found to be insecticidal to adult B. argentifolii. 相似文献
276.
Various fluorescent conjugated lectins have been used for the detection of glycoconjugates on nematode surfaces under light microscopy. Several problems have been experienced with these reagents including penetration of the cuticle by fluorescent lectins, non-glycoconjugate specificity, strong nematode autofluorescence at the emission wavelength of the fluorescent dye, and prevention of persistent visualization due to rapid quenching of the fluorescent components. Gold-conjugated reagents combined with silver enhancement alleviated these difficulties when working with three phytonematode species (Heterodera avenae, H. latipons, and Meloidogyne javanica) and two entomopathogenic species (Steinernema carpocapsae and S. glaseri) under light-microscopy visualization of binding by fluorescent lectins and neoglycoproteins. Moreover, gold-conjugated reagents resulted in stable bindings that enabled long-term observations. 相似文献
277.
278.
Tosikazu Amano Hiromi Kawabata Katsutoshi Yoshizato 《Development, growth & differentiation》1995,37(2):211-220
The skin of an adult frog of Xenopus laevis was characterized by the reactivity of 20 lectins. The lectins were classified into six groups in their binding to the epidermal cells: Lycopersicon esculentum lectin (LEL)-type which was positive for all epidermal cells; Pisum sativum agglutinin (PSA)-type for stratum germinativum; succinylated wheat germ agglutinin (sWGA)-type for strata spinosum, granulosum and corneum; Dolichos biflorus agglutinin (DBA)-type for strata germinativum and spinosum; peanut agglutinin (PNA)-type for stratum spinosum; and Ulex europaeus agglutinin (UEA-I)-type for strata granulosum and corneum. PSA and sWGA were utilized as markers of mitotically active germinative cells and the differentiated cells of the epidermis, respectively, to describe the metamorphic conversion of larval epidermal cells to adult type. PSA stained all epidermal cells of tadpoles before metamorphic climax. At the end of metamorphosis, PSA-positive cells were restricted to cells in the basal layer of body epidermis while all the tail epidermis remained PSA-positive. The other cell marker, sWGA, only stained apical cells in tadpole epidermis. During the metamorphic climax, sWGA-positive cells appeared in the cells beneath the stratum corneum of the body region, but not in the tail region. The present study demonstrates that PSA and sWGA are useful to investigate metamorphic changes in tadpole epidermal cells. 相似文献
279.
The three-dimensional structure of demetallized concanavalin A has been determined at 2.5 Å resolution and refined to a crystallographic R-factor of 18%. The lectin activity of concanavalin A requires the binding of both a transition metal ion, generally Mn2+, and a Ca2+ ion in two neighboring sites in close proximity to the carbohydrate binding site. Large structural differences between the native and the metal-free lectin are observed in the metal-binding region and consequently for the residues involved in the specific binding of saccharides. The demetallization invokes a series of conformational changes in the protein backbone, apparently initiated mainly by the loss of the calcium ion. Most of the Mn2+ ligands retain their position, but the Ca2+ binding site is destroyed. The Ala207-Asp208 peptide bond, in the β-strand neighboring the metal-binding sites, undergoes a cis to trans isomerization. The cis conformation for this bond is a highly conserved feature among the leguminous lectins and is critically maintained by the Ca2+ ion in metal-bound concanavalin A. A further and major change adjacent to the isomerized bond is an expansion of the loop containing the monosaccharide ligand residues Leu99 and Tyr100. The dispersion of the ligand residues for the monosaccharide binding site (Asn14, Agr228, Asp208, Leu99, and Tyr100) in metalfree concanavalin A abolishes the lectin's ability to bind saccharides. Since the quaternary structure of legume lectins is essential to their biological role, the tetramer formation was analyzed. In the crystal (pH 5), the metal-free concanavalin A dimers associate into a tetramer that is similar to the native one, but with a drastically reduced number of inter-dimer interactions. This explains the tetramer dissociation into dimers below pH values of 6.5. © 1995 Wiley-Liss, Inc. 相似文献
280.
Hirotaka Yamamoto Yoichi Kaneko David Vandermulen Donna Kersey Edward Mkrdichian Leonard Cerullo Jan Leestma Joseph R. Moskal 《Glycoconjugate journal》1995,12(6):848-856
The expression of CMP-NeuAc: Gal1,4GlcNAc 2,6 sialyltransferase (2,6-ST) [EC 2.4.99.1] and glycoproteins bearing 2,6-linked sialic acids were examined in primary human brain tumours and cell lines. 79% (19/24) of the meningiomas expressed 2,6-ST mRNA, 42% (10/24) of which showed very high expression. 2,6-ST mRNA expression was undetectable in normal brain tissue. In contrast, only 1/13 of the gliomas examined expressed detectable 2,6-ST mRNA. Metastases to the brain did not express measurable amounts of 2,6-ST mRNA. Less expression was found in malignant (i.e., anaplastic) compared to benign (i.e. meningothelial) meningiomas. Two-dimensional SDS-PAGE of glioma and meningioma proteins, followed bySambucus nigra lectin staining, revealed the presence of a glycoprotein bearing 2,6-linked sialic acids,M
r=53 kDa and a pI=7.0 (MEN-1) that appeared in all seven of the meningiomas examined, but was expressed at barely detectable levels, if at all, in seven out of the seven glioblastomas examined. Thus, decreased 2,6-ST expression may play a role in the aggressive nature of anaplastic meningiomas, but appears to be virtually absent in all tumours of glial origin. 相似文献