全文获取类型
收费全文 | 1585篇 |
免费 | 64篇 |
专业分类
1649篇 |
出版年
2023年 | 2篇 |
2022年 | 5篇 |
2021年 | 14篇 |
2020年 | 7篇 |
2019年 | 5篇 |
2018年 | 14篇 |
2017年 | 10篇 |
2016年 | 26篇 |
2015年 | 42篇 |
2014年 | 53篇 |
2013年 | 69篇 |
2012年 | 122篇 |
2011年 | 86篇 |
2010年 | 70篇 |
2009年 | 66篇 |
2008年 | 95篇 |
2007年 | 106篇 |
2006年 | 86篇 |
2005年 | 110篇 |
2004年 | 101篇 |
2003年 | 112篇 |
2002年 | 90篇 |
2001年 | 18篇 |
2000年 | 15篇 |
1999年 | 16篇 |
1998年 | 41篇 |
1997年 | 13篇 |
1996年 | 21篇 |
1995年 | 16篇 |
1994年 | 21篇 |
1993年 | 20篇 |
1992年 | 14篇 |
1991年 | 12篇 |
1990年 | 7篇 |
1989年 | 9篇 |
1988年 | 7篇 |
1986年 | 9篇 |
1985年 | 11篇 |
1984年 | 10篇 |
1983年 | 10篇 |
1982年 | 12篇 |
1981年 | 15篇 |
1980年 | 10篇 |
1979年 | 6篇 |
1978年 | 10篇 |
1977年 | 5篇 |
1976年 | 9篇 |
1975年 | 7篇 |
1974年 | 5篇 |
1966年 | 2篇 |
排序方式: 共有1649条查询结果,搜索用时 15 毫秒
991.
992.
Gaudillière JP 《Journal of the history of biology》2006,39(4):737-764
During the late 1940s and 1950s, radioisotopes became important resources for biological and medical research. This article explores the strategies used by French researchers to get access to this material, either from the local Atomic Energy Commission (CEA) or from suppliers in the United States or United Kingdom. It focuses on two aspects of this process: the transatlantic circulation of both isotopes and associated instrumentation; the regulation of use and access by the administrative bodies governing research in France. Analyzing the investigations conducted within laboratories associated either with the atomic energy agency or with the local National Institute of Health (INH), the paper discusses the part played by the new tools in the postwar transformation of biomedical research. It contrasts the INH successful development of biological studies and metabolic tracing with the mixed results of CEA in advancing cancer radiotherapy, thus highlighting locally defined “normal paths” to radiobiology. 相似文献
993.
The purinergic receptor P2X7 is widely expressed in epithelial cells. This receptor shares in common with the other P2X receptors the ability to form a non-selective cation channel. On the other hand, the COOH terminus of P2X7 seems to allow this receptor to couple to a spectrum of downstream effectors responsible for the regulation of cell death and pore formation among other functions. However, the coupling of P2X7 to these downstream effectors, as well as the identity of possible adapters directly interacting with the receptor, remains poorly understood. Here we review the ability of P2X7 to activate phospholipid signalling pathways in epithelial cells and propose this step as a possible link between the receptor and other downstream effectors. The P2X7 ability to control the cellular levels of several lipid messengers (PA, AA, DAG, ceramide, etc.) through the modulation of phospholipases (C, A2, D) and neutral sphingomyelinase is described. These pathways are sometimes regulated independently of the channel function of the receptor. Recent data concerning P2X7 localization in lipid rafts is also discussed in relation to the coupling to these pathways and dissociation from channel function. 相似文献
994.
Dominique Legrand Keveen Vigié Elias A Said Elisabeth Elass Maryse Masson Marie-Christine Slomianny Mathieu Carpentier Jean-Paul Briand Jo?l Mazurier Ara G Hovanessian 《European journal of biochemistry》2004,271(2):303-317
Lactoferrin (Lf), a multifunctional molecule present in mammalian secretions and blood, plays important roles in host defense and cancer. Indeed, Lf has been reported to inhibit the proliferation of cancerous mammary gland epithelial cells and manifest a potent antiviral activity against human immunodeficiency virus and human cytomegalovirus. The Lf-binding sites on the cell surface appear to be proteoglycans and other as yet undefined protein(s). Here, we isolated a Lf-binding 105 kDa molecular mass protein from cell extracts and identified it as human nucleolin. Medium-affinity interactions ( approximately 240 nm) between Lf and purified nucleolin were further illustrated by surface plasmon resonance assays. The interaction of Lf with the cell surface-expressed nucleolin was then demonstrated through competitive binding studies between Lf and the anti-human immunodeficiency virus pseudopeptide, HB-19, which binds specifically surface-expressed nucleolin independently of proteoglycans. Interestingly, binding competition studies between HB-19 and various Lf derivatives in proteoglycan-deficient hamster cells suggested that the nucleolin-binding site is located in both the N- and C-terminal lobes of Lf, whereas the basic N-terminal region is dispensable. On intact cells, Lf co-localizes with surface nucleolin and together they become internalized through vesicles of the recycling/degradation pathway by an active process. Morever, a small proportion of Lf appears to translocate in the nucleus of cells. Finally, the observations that endocytosis of Lf is inhibited by the HB-19 pseudopeptide, and the lack of Lf endocytosis in proteoglycan-deficient cells despite Lf binding, point out that both nucleolin and proteoglycans are implicated in the mechanism of Lf endocytosis. 相似文献
995.
In flaxseed hulls, lignans are present in an oligomeric structure. Secoisolariciresinol diglucoside (SDG), ester-linked to hydroxy-methyl-glutaric acid (HMGA), forms the backbone of this lignan macromolecule. The hydroxycinnamic acids p-coumaric acid glucoside (CouAG) and ferulic acid glucoside (FeAG) are also part of the lignan macromolecule. However, their position and type of linkage are still unknown. The aim of this study was to investigate how CouAG and FeAG are linked within the lignan macromolecule from flaxseed hulls. Fragments of the lignan macromolecule were obtained by partial saponification. After isolation of the fragments by preparative RP-HPLC, several key structures were identified by MS and NMR. Within the lignan macromolecule, CouAG is attached to the C-6 position of a glucosyl moiety of SDG. FeA is linked to the C-2 position of a glucosyl moiety of SDG. FeAG is ester-linked within the lignan macromolecule with its carboxyl group, but it remains unclear whether FeAG links to the C-2 or C-6 position of SDG. Attachment of HMGA to the glucosyl moiety of CouAG or FeAG was not observed. The results clearly show that within the lignan macromolecule, the hydroxycinnamic acids are linked directly via an ester bond to the glucosyl moiety of SDG. 相似文献
996.
Dumestre-Pérard C Lamy B Aldebert D Lemaire-Vieille C Grillot R Brion JP Gagnon J Cesbron JY 《Journal of immunology (Baltimore, Md. : 1950)》2008,181(10):7100-7105
Innate immunity is the major host defense against invasive aspergillosis. To determine whether the collectin mannan-binding lectin (MBL) is involved in the initial protective immunity through complement activation against opportunistic fungal infections caused by Aspergillus, we performed in vitro studies on 29 different strains of Aspergillus conidia from five different species. Incubation of Aspergillus conidia in human normal serum leads to activation of the alternative pathway, whereas neither the classical nor the lectin pathways through C4 and C2 cleavage are activated. Complement response to conidia was investigated using a MBL-deficient serum and reconstitution experiments were conducted with MBL/MASPs complexes. We found that MBL can directly support C3 activation by a C2 bypass mechanism. Finally, a stronger activation of the alternative pathway was observed for the clinical strains isolated from patients with invasive aspergillosis, compared with the environmental strains. 相似文献
997.
998.
Murielle Bouchez-Naïtali Jean-Paul Vandecasteele 《World journal of microbiology & biotechnology》2008,24(9):1901-1907
The roles of the extracellular biosurfactants produced by two bacterial strains, Pseudomonas aeruginosa GL1 and Rhodococcus equi Ou2, in hexadecane uptake and biodegradation were compared. For this purpose, cell hydrophobicity and production of glycolipidic
biosurfactants were evaluated during bacterial growth on hexadecane, as well the effects of these biosurfactants on culture
supernatants properties i.e., surface and interfacial tensions, and emulsification and pseudosolubilization capacities. The
results showed that the role of biosurfactants was different in these two strains and was directly related to the hydrophobicity
of the bacterial cells concerned. Extracellular biosurfactants produced by strain R. equi Ou2 had only a minor role in hexadecane degradation. Direct interfacial accession appeared to be the main mechanism for hexadecane
uptake by the hydrophobic cells of strain R. equi Ou2. On the contrary, the biosurfactants produced by P. aeruginosa GL1 were required for growth on hexadecane, and their pseudosolubilization capacity rather than their emulsification capacity
was involved in substrate degradation, allowing uptake from hexadecane micelles by the hydrophilic cells of this bacterium.
The roles of biosurfactants thus differ widely among bacteria degrading hydrophobic compounds.
J.-P. Vandecasteele—in retirement 相似文献
999.
Chomilier J Lamarine M Mornon JP Torres JH Eliopoulos E Papandreou N 《Comptes rendus biologies》2004,327(5):431-443
The folding process of a set of 42 proteins, representative of the various folds, has been simulated by means of a Monte Carlo method on a discrete lattice, using two different potentials of mean force. Multiple compact fragments of contiguous residues are formed in the simulation, stable in composition, but not in geometry. During time, the number of fragments decreases until one final compact globular state is reached. We focused on the early steps of the folding in order to evidence the maximum number of fragments, provided they are sufficiently stable in sequence. A correlation has been established between these proto fragments and regular secondary-structure elements, whatever their nature, alpha helices or beta strands. Quantitatively, this is revealed by an overall mean one-residue quality factor of nearly 60%, which is better for proteins mainly composed of alpha helices. The correspondence between the number of fragments and the number of secondary-structure elements is of 77% and the regions separating successive fragments are mainly located in loops. Besides, hydrophobic clusters deduced from HCA correspond to fragments with an equivalent accuracy. These results suggest that folding pathways do not contain structurally static intermediate. However, since the beginning of folding, most residues that will later form one given secondary structure are kept close in space by being involved in the same fragment. This aggregation may be a way to accelerate the formation of the native state and enforces the key role played by hydrophobic residues in the formation of the fragments, thus in the folding process itself. 相似文献
1000.
Márquez V Fröhlich T Armache JP Sohmen D Dönhöfer A Mikolajka A Berninghausen O Thomm M Beckmann R Arnold GJ Wilson DN 《Journal of molecular biology》2011,405(5):1215-1232
Protein synthesis occurs in macromolecular particles called ribosomes. All ribosomes are composed of RNA and proteins. While the protein composition of bacterial and eukaryotic ribosomes has been well-characterized, a systematic analysis of archaeal ribosomes has been lacking. Here we report the first comprehensive two-dimensional PAGE and mass spectrometry analysis of archaeal ribosomes isolated from the thermophilic Pyrobaculum aerophilum and the thermoacidophilic Sulfolobus acidocaldarius Crenarchaeota. Our analysis identified all 66 ribosomal proteins (r-proteins) of the P. aerophilum small and large subunits, as well as all but two (62 of 64; 97%) r-proteins of the S. acidocaldarius small and large subunits that are predicted genomically. Some r-proteins were identified with one or two lysine methylations and N-terminal acetylations. In addition, we identify three hypothetical proteins that appear to be bona fide r-proteins of the S. acidocaldarius large subunit. Dissociation of r-proteins from the S. acidocaldarius large subunit indicates that the novel r-proteins establish tighter interactions with the large subunit than some integral r-proteins. Furthermore, cryo electron microscopy reconstructions of the S. acidocaldarius and P. aerophilum 50S subunits allow for a tentative localization of the binding site of the novel r-proteins. This study illustrates not only the potential diversity of the archaeal ribosomes but also the necessity to experimentally analyze the archaeal ribosomes to ascertain their protein composition. The discovery of novel archaeal r-proteins and factors may be the first step to understanding how archaeal ribosomes cope with extreme environmental conditions. 相似文献