全文获取类型
收费全文 | 1349篇 |
免费 | 95篇 |
出版年
2023年 | 11篇 |
2022年 | 8篇 |
2021年 | 27篇 |
2020年 | 23篇 |
2019年 | 31篇 |
2018年 | 26篇 |
2017年 | 31篇 |
2016年 | 37篇 |
2015年 | 66篇 |
2014年 | 76篇 |
2013年 | 73篇 |
2012年 | 93篇 |
2011年 | 101篇 |
2010年 | 79篇 |
2009年 | 62篇 |
2008年 | 79篇 |
2007年 | 67篇 |
2006年 | 66篇 |
2005年 | 62篇 |
2004年 | 68篇 |
2003年 | 54篇 |
2002年 | 44篇 |
2001年 | 22篇 |
2000年 | 28篇 |
1999年 | 18篇 |
1998年 | 17篇 |
1997年 | 9篇 |
1996年 | 12篇 |
1995年 | 4篇 |
1994年 | 9篇 |
1993年 | 4篇 |
1992年 | 6篇 |
1991年 | 11篇 |
1990年 | 7篇 |
1989年 | 14篇 |
1988年 | 7篇 |
1987年 | 7篇 |
1986年 | 7篇 |
1985年 | 8篇 |
1984年 | 8篇 |
1983年 | 3篇 |
1982年 | 3篇 |
1981年 | 5篇 |
1980年 | 4篇 |
1979年 | 4篇 |
1977年 | 4篇 |
1976年 | 6篇 |
1975年 | 5篇 |
1974年 | 7篇 |
1970年 | 5篇 |
排序方式: 共有1444条查询结果,搜索用时 15 毫秒
71.
72.
Paraoan L Ratnayaka A Spiller DG Hiscott P White MR Grierson I 《Traffic (Copenhagen, Denmark)》2004,5(11):884-895
Cystatin C is abundantly expressed by the retinal pigment epithelium (RPE) of the eye. Targeting of cystatin C to the Golgi apparatus and processing through the secretory pathway of RPE cells are dependent upon a 26-amino acid signal sequence of precursor cystatin C. A variant with an alanine (A) to threonine (T) mutation in the penultimate amino acid of the signal sequence (A25T) was recently correlated with increased risk of developing exudative age-related macular degeneration. The biochemical consequence of the A25T mutation upon targeting of the protein is reported here. Targeting and trafficking of full-length mutant (A25T) precursor cystatin C-enhanced green fluorescent protein fusion protein were studied in living, cultured retinal pigment epithelial and HeLa cells. Confocal microscopy studies were substantiated by immunodetection. In striking contrast to wild-type precursor cystatin C fusion protein conspicuously targeted to the Golgi apparatus, the threonine variant was associated principally with mitochondria. Some diffuse fluorescence was also observed throughout the cytoplasm and nucleus (but not nucleoli). Secretion of fusion protein derived from the threonine variant was reduced by approximately 50% compared with that of the wild-type cystatin C fusion protein. Expression of the variant fusion protein did not appear to impair expression or secretion of endogenous cystatin C. 相似文献
73.
Designing new materials from wheat protein 总被引:4,自引:0,他引:4
Woerdeman DL Veraverbeke WS Parnas RS Johnson D Delcour JA Verpoest I Plummer CJ 《Biomacromolecules》2004,5(4):1262-1269
We recently discovered that wheat gluten could be formed into a tough, plasticlike substance when thiol-terminated, star-branched molecules are incorporated directly into the protein structure. This discovery offers the exciting possibility of developing biodegradable high-performance engineering plastics and composites from renewable resources that are competitive with their synthetic counterparts. Wheat gluten powder is available at a cost of less than dollars 0.5/lb, so if processing costs can be controlled, an inexpensive alternative to synthetic polymers may be possible. In the present work, we demonstrate the ability to toughen an otherwise brittle protein-based material by increasing the yield stress and strain-to-failure, without compromising stiffness. Water absorption results suggest that the cross-link density of the polymer is increased by the presence of the thiol-terminated, star-branched additive in the protein. Size-exclusion high performance liquid chromatography data of molded tri-thiol-modified gluten are consistent with that of a polymer that has been further cross-linked when compared directly with unmodified gluten, handled under identical conditions. Remarkably, the mechanical properties of our gluten formulations stored in ambient conditions were found to improve with time. 相似文献
74.
Morrow MD Higgs D Kennedy CJ 《Comparative biochemistry and physiology. Toxicology & pharmacology : CBP》2004,137(2):143-154
Juvenile rainbow trout (Oncorhynchus mykiss) were fed one of three isoenergetic diets varying in protein (35-55%) and lipid content (8-18%), at full satiation levels or half rations for 6 weeks in order to investigate the effects of diet on baseline stress parameters and biotransformation enzyme activity. Growth was greatest in fish fed to satiation on a low protein and high lipid diet. Stress parameters, including plasma lactate, glucose and cortisol concentrations were not significantly affected by dietary treatment or ration. Basal biotransformation enzymes, including glutathione S-transferase (GST) and ethoxyresorufin O-deethylase (EROD) activity, were also unaffected by dietary treatment. Fish exposed to the biotransformation enzyme inducer beta-naphthoflavone did not exhibit an alteration in stress indicators or GST activity; however, EROD activity was increased (87- to 210-fold) in fish receiving all diets and rations. The results of the present study indicate that, unlike mammals, fish may be more recalcitrant to different levels of ingestion of isoenergetic diets varying in protein and lipid concentration with respect to stress responses and the maintenance of basal titers of biotransformation enzymes and their induction. 相似文献
75.
Anti-IL-13 monoclonal antibody inhibits airway hyperresponsiveness, inflammation and airway remodeling 总被引:8,自引:0,他引:8
Yang G Volk A Petley T Emmell E Giles-Komar J Shang X Li J Das AM Shealy D Griswold DE Li L 《Cytokine》2004,28(6):224-232
Asthma is a chronic inflammatory disease characterized by reversible bronchial constriction, pulmonary inflammation and airway remodeling. Current standard therapies for asthma provide symptomatic control but fail to target the underlying disease pathology. Furthermore, no therapeutic agent is effective in preventing airway remodeling. Interleukin 13 (IL-13) is a pleiotropic cytokine produced mainly by T cells. A substantial amount of evidence suggests that IL-13 plays a critical role in the pathogenesis of asthma. Therefore, a neutralizing anti-IL-13 monoclonal antibody could provide therapeutic benefits to asthmatic patients. To test the concept we have generated a neutralizing rat anti-mouse IL-13 monoclonal antibody, and evaluated its effects in a chronic mouse model of asthma. Chronic asthma-like response was induced in ovalbumin (OVA) sensitized mice by repeated intranasal OVA challenges. After weeks of challenge, mice developed airway hyperresponsiveness (AHR) to methacholine stimulation, severe airway inflammation, hyper mucus production, and subepithelial fibrosis. When given at the time of each intranasal OVA challenge, anti-IL-13 antibody significantly suppressed AHR, eosinophil infiltration, proinflammatory cytokine/chemokine production, serum IgE, and most interestingly, airway remodeling. Taken together, these results strongly suggest that a neutralizing anti-human IL-13 monoclonal antibody could be an effective therapeutic agent for asthma. 相似文献
76.
77.
Brown JW Echeverria M Qu LH Lowe TM Bachellerie JP Hüttenhofer A Kastenmayer JP Green PJ Shaw P Marshall DF 《Nucleic acids research》2003,31(1):432-435
The Plant snoRNA database (http://www.scri.sari.ac.uk/plant_snoRNA/) provides information on small nucleolar RNAs from Arabidopsis and eighteen other plant species. Information includes sequences, expression data, methylation and pseudouridylation target modification sites, initial gene organization (polycistronic, single gene and intronic) and the number of gene variants. The Arabidopsis information is divided into box C/D and box H/ACA snoRNAs, and within each of these groups, by target sites in rRNA, snRNA or unknown. Alignments of orthologous genes and gene variants from different plant species are available for many snoRNA genes. Plant snoRNA genes have been given a standard nomenclature, designed wherever possible, to provide a consistent identity with yeast and human orthologues. 相似文献
78.
Five microsatellite DNA markers were isolated and used to quantify population genetic structure among a subset of UK populations of the Adonis blue (Polyommatus bellargus Rottemburg). Specifically, whether population size, degree of isolation or history of bottlenecking in 1976-1978 can explain current patterns of genetic variation. The butterfly is at its northern range limit in the UK, where it exists as a highly fragmented metapopulation on isolated pockets of calcareous grassland. Most populations were affected by a severe bottleneck in the late 1970s, when a drought caused the host plant (Hippocrepis comosa) to wilt. Mantel tests and spatial autocorrelation analysis indicated a significant effect of isolation by distance among the UK populations, a relationship that broke down at greater geographical scales (> 23.85 km), probably because of large areas of unsuitable habitat presenting barriers to gene flow. Similarly, amova revealed that variation among geographical regions was almost double that observed within regions. Larger populations were found to support significantly higher levels of genetic diversity, suggesting that small populations may lose genetic diversity through drift. If, as in other butterfly species, low genetic diversity increases the probability of population extinction, then these populations are likely to be under threat. Neither isolation nor a history of bottlenecks appeared to influence genetic diversity. The results indicate that adequate population size a crucial factor in the conservation of genetic diversity in P. bellargus in the UK. 相似文献
79.
Green NJ Xiang J Chen J Chen L Davies AM Erbe D Tam S Tobin JF 《Bioorganic & medicinal chemistry》2003,11(13):2991-3013
The interaction of co-stimulatory molecules on T cells with B7 molecules on antigen presenting cells plays an important role in the activation of naive T cells. Consequently, agents that disrupt these interactions should have applications in treatment of transplant rejection as well as autoimmune diseases. To this end, specific small molecule inhibitors of human B7.1 were identified and characterized. Herein, we report the identification of potent small molecule inhibitors of the B7.1-CD28 interaction. In a high-throughput screen we identified several leads that prevented the interaction of B7.1 with CD28 with activities in the nanomolar to low micromolar range. One of these, the dihydrodipyrazolopyridinone 1, was subsequently shown to bind the V-like domain of human B7.1 at equimolar stoichiometry. With this as a starting point, we report here the synthesis and initial in vitro structure-activity relationships of a series of these compounds. 相似文献
80.
Buonaccorsi JP Elkinton J Koenig W Duncan RP Kelly D Sork V 《Journal of theoretical biology》2003,224(1):107-114
Mast seeding, or masting, is the variable production of flowers, seeds, or fruit across years more or less synchronously by individuals within a population. A critical issue is the extent to which temporal variation in seed production over a collection of individuals can be viewed as arising from a combination of individual variation and synchrony among individuals. Studies of masting typically quantify such variation in terms of the coefficient of variation (CV). In this paper we examine mathematically how the population CV relates to the mean individual CV and synchrony, concluding that the relationship is a complex one which cannot isolate an overall measure of synchrony, and involves additional factors, principally the number of plants sampled and the mean productivity per plant. Our development suggests some simple approximate relationships of population CV to individual variability, synchrony and the number of individuals. These were found to fit quite well when applied to data from 59 studies which included seed production at the individual level. 相似文献