全文获取类型
收费全文 | 987篇 |
免费 | 73篇 |
学科分类
生物科学 | 1060篇 |
出版年
2023年 | 3篇 |
2022年 | 3篇 |
2021年 | 26篇 |
2020年 | 13篇 |
2019年 | 10篇 |
2018年 | 23篇 |
2017年 | 21篇 |
2016年 | 34篇 |
2015年 | 56篇 |
2014年 | 57篇 |
2013年 | 57篇 |
2012年 | 87篇 |
2011年 | 79篇 |
2010年 | 56篇 |
2009年 | 45篇 |
2008年 | 56篇 |
2007年 | 73篇 |
2006年 | 58篇 |
2005年 | 45篇 |
2004年 | 57篇 |
2003年 | 52篇 |
2002年 | 31篇 |
2001年 | 8篇 |
2000年 | 6篇 |
1999年 | 5篇 |
1998年 | 10篇 |
1997年 | 4篇 |
1996年 | 7篇 |
1995年 | 8篇 |
1994年 | 7篇 |
1993年 | 3篇 |
1992年 | 2篇 |
1991年 | 3篇 |
1990年 | 2篇 |
1989年 | 2篇 |
1988年 | 4篇 |
1987年 | 3篇 |
1986年 | 4篇 |
1985年 | 2篇 |
1984年 | 2篇 |
1983年 | 4篇 |
1982年 | 2篇 |
1981年 | 3篇 |
1980年 | 5篇 |
1979年 | 5篇 |
1977年 | 5篇 |
1974年 | 3篇 |
1972年 | 2篇 |
1970年 | 2篇 |
1969年 | 2篇 |
排序方式: 共有1060条查询结果,搜索用时 15 毫秒
91.
Prats-Puig A Bassols J Bargalló E Mas-Parareda M Ribot R Soriano-Rodríguez P Berengüí À Díaz M de Zegher F Ibánez L López-Bermejo A 《Obesity (Silver Spring, Md.)》2011,19(9):1905-1907
Omentin-1 is a recently recognized adipokine primarily originating in visceral adipose tissue. We posited that circulating omentin-1 could be an early marker of metabolic dysfunction. To this end, we examined the associations between circulating omentin-1, body fat (bioelectric impedance), an endocrine-metabolic profile (homeostasis model assessment for insulin resistance (HOMA(IR)), serum lipids, high-molecular-weight (HMW) adiponectin and blood pressure (BP)) and family history of obesity and diabetes in asymptomatic prepubertal children (n = 161; 77 boys and 84 girls; age 7 ± 1 year) with a normal distribution of height and weight. Increased circulating omentin-1 was associated with a poorer metabolic profile, with relatively higher HOMA(IR), fasting triacylglycerol, BP and familial prevalence of diabetes (all P < 0.005 to P < 0.0001), and relatively lower fraction of HMW adiponectin (P < 0.005), whereas no relationship was found with body weight or fat or with family history of obesity. All these associations were independent of age, gender and fat mass. In conclusion, circulating omentin-1 may become a marker of metabolic dysfunction integrating insulin sensitivity, markers of adipose-tissue metabolism and BP as early as in prepubertal childhood. 相似文献
92.
Bohu??ObertEmail author László?Szabó Judit?Mitykó Anna?Pre?ová Beáta?Barnabás 《In vitro cellular & developmental biology. Plant》2005,41(6):775-782
Summary In tis androgenic response, maize is considered to be a recalcitrant plant. We used mechanically isolated microspores of maize
genotype A18 to establish a responsive microspore culture of maize. Morphological events occurring during the first days of
maize androgenesis in a microspore culture were observed and described, and some morphological markers for distinguishing
between embryogenic microspores and nonembryogenic microspores were identified. It was found that the enlargement of microspores
during the first days in culture and the ‘star-like’ organization of the cytoplasm inside the microspore are connected with
reprogramming of the developmental pathway in maize microspores. Some differences were also found in the surface wall architecture
of embryogenic microspores. Fertile plants were successfully recovered from microspore-originated structures. 相似文献
93.
Theoretical calculations on hydrogenase kinetics: explanation of the lag phase and the enzyme concentration dependence of the activity of hydrogenase uptake 下载免费PDF全文
Two models of the hydrogenase reaction cycle were investigated by means of theoretical calculations and model simulations. The first model is the widely accepted triangular hydrogenase reaction cycle with minor modifications; the second is a modified triangular model, where we have introduced an autocatalytic step into the reaction cycle. Both models include a one-step activation reaction. The theoretical calculations and model simulations corroborate the assumed autocatalytic reaction step concluded from the experimental characteristics of the hydrogenase reaction. 相似文献
94.
95.
Clostridium difficile is a bacterium that causes disease of the large intestine, particularly after treatment with antibiotics. The bacterium produces two toxins (A and B) that are responsible for the pathology of the disease. In addition, a number of bacterial virulence factors associated with adhesion to the gut have previously been identified, including the cell wall protein Cwp66, the high-molecular weight surface layer protein (HMW-SLP) and the flagella. As the genome sequence predicts many other cell wall associated proteins, we have investigated the diversity of proteins in cell wall extracts, with the aim of identifying further virulence factors. We have used a number of methods to remove the proteins associated with the cell wall of C. difficile. Two of the resulting extracts, obtained using low pH glycine treatment and lysozyme digestion of the cell wall, have been analysed in detail by two-dimensional electrophoresis and mass spectrometry. One hundred and nineteen spots, comprising 49 different proteins, have been identified. The two surface layer proteins (SLPs) are the most abundant proteins, and we have also found components of the flagellum. Interestingly, we have also determined that a number of paralogs of the HMW-SLP are expressed, and these could represent targets for further investigation as virulence factors. 相似文献
96.
Molecular defects in cardiac myofibrillar proteins due to thyroid hormone imbalance and diabetes 总被引:1,自引:0,他引:1
Machackova J Barta J Dhalla NS 《Canadian journal of physiology and pharmacology》2005,83(12):1071-1091
The heart very often becomes a victim of endocrine abnormalities such as thyroid hormone imbalance and insulin deficiency, which are manifested in a broad spectrum of cardiac dysfunction from mildly compromised function to severe heart failure. These functional changes in the heart are largely independent of alterations in the coronary arteries and instead reside at the level of cardiomyocytes. The status of cardiac function reflects the net of underlying subcellular modifications induced by an increase or decrease in thyroid hormone and insulin plasma levels. Changes in the contractile and regulatory proteins constitute molecular and structural alterations in myofibrillar assembly, called myofibrillar remodeling. These alterations may be adaptive or maladaptive with respect to the functional and metabolic demands on the heart as a consequence of the altered endocrine status in the body. There is a substantial body of information to indicate alterations in myofibrillar proteins including actin, myosin, tropomyosin, troponin, titin, desmin, and myosin-binding protein C in conditions such as hyperthyroidism, hypothyroidism, and diabetes. The present article is focussed on discussion how myofibrillar proteins are altered in response to thyroid hormone imbalance and lack of insulin or its responsiveness, and how their structural and functional changes explain the contractile defects in the heart. 相似文献
97.
Bánfi B Tirone F Durussel I Knisz J Moskwa P Molnár GZ Krause KH Cox JA 《The Journal of biological chemistry》2004,279(18):18583-18591
NADPH oxidase 5 (NOX5) is a homologue of the gp91(phox) subunit of the phagocyte NADPH oxidase. NOX5 is expressed in lymphoid organs and testis and distinguished from the other NADPH oxidases by its unique N terminus, which contains three canonical EF-hands, Ca(2+)-binding domains. Upon heterologous expression, NOX5 was shown to generate superoxide in response to intracellular Ca(2+) elevations. In this study, we have analyzed the mechanism of Ca(2+) activation of NOX5. In a cell-free system, Ca(2+) elevations triggered superoxide production by NOX5 (K(m) = 1.06 microm) in an NADPH- and FAD-dependent but cytosol-independent manner. That result indicated a role for the N-terminal EF-hands in NOX5 activation. Therefore, we generated recombinant proteins of NOX5 N terminus and investigated their interactions with Ca(2+). Flow dialysis experiments showed that NOX5 N terminus contained four Ca(2+)-binding sites and allowed us to define the hitherto unidentified fourth, non-canonical EF-hand. The EF-hands of NOX5 formed two pairs: the very N-terminal pair had relatively low affinity for Ca(2+), whereas the more C-terminal pair bound Ca(2+) with high affinity. Ca(2+) binding caused a marked conformation change in the N terminus, which exposed its hydrophobic core, and became able to bind melittin, a model peptide for calmodulin targets. Using a pull-down assay, we demonstrate that the regulatory N terminus and the catalytic C terminus of NOX5 interact in a Ca(2+)-dependent way. Our results indicate that the Ca(2+)-induced conformation change of NOX5 N terminus led to enzyme activation through an intra-molecular interaction. That represents a novel mechanism of activation among NAD(P)H oxidases and Ca(2+)-activated enzymes. 相似文献
98.
Budai B Hitre E Adleff V Czeglédi F Gyergyay F Láng I Kralovánszky J 《Magyar onkologia》2004,48(3):253-257
The authors investigated the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism in 101 metastatic colorectal cancer patients treated with 5-fluoropyrimidine-based therapy and in 196 healthy individuals by PCR-RFLP method. There was no significant difference in genotype distribution of patients and healthy controls, and between subgroups investigated according to clinical parameters (age, gender, tumor location, grade and treatment type). However, after a 3-30 (median 18.5) months follow-up the survival of patients with T allele proved to be better than that of patients with wild type (CC) genotype (p=0.036). In case of CT and TT genotypes the survival of patients receiving only first line therapy was significantly shorter than that of patients receiving more lines of treatment (p=0.015). Determination of MTHFR C677T polymorphism has prognostic value in case of patients with metastatic colorectal cancer receiving 5-fluoropyrimidine-based therapy, and may help in designing the individual (group) tailored therapy. 相似文献
99.
100.
Mutations in ACY1, the gene encoding aminoacylase 1, cause a novel inborn error of metabolism 下载免费PDF全文
Sass JO Mohr V Olbrich H Engelke U Horvath J Fliegauf M Loges NT Schweitzer-Krantz S Moebus R Weiler P Kispert A Superti-Furga A Wevers RA Omran H 《American journal of human genetics》2006,78(3):401-409
N-terminal acetylation of proteins is a widespread and highly conserved process. Aminoacylase 1 (ACY1; EC 3.5.14) is the most abundant of the aminoacylases, a class of enzymes involved in hydrolysis of N-acetylated proteins. Here, we present four children with genetic deficiency of ACY1. They were identified through organic acid analyses using gas chromatography-mass spectrometry, revealing increased urinary excretion of several N-acetylated amino acids, including the derivatives of methionine, glutamic acid, alanine, leucine, glycine, valine, and isoleucine. Nuclear magnetic resonance spectroscopy analysis of urine samples detected a distinct pattern of N-acetylated metabolites, consistent with ACY1 dysfunction. Functional analyses of patients' lymphoblasts demonstrated ACY1 deficiency. Mutation analysis uncovered recessive loss-of-function or missense ACY1 mutations in all four individuals affected. We conclude that ACY1 mutations in these children led to functional ACY1 deficiency and excretion of N-acetylated amino acids. Questions remain, however, as to the clinical significance of ACY1 deficiency. The ACY1-deficient individuals were ascertained through urine metabolic screening because of unspecific psychomotor delay (one subject), psychomotor delay with atrophy of the vermis and syringomyelia (one subject), marked muscular hypotonia (one subject), and follow-up for early treated biotinidase deficiency and normal clinical findings (one subject). Because ACY1 is evolutionarily conserved in fish, frog, mouse, and human and is expressed in the central nervous system (CNS) in human, a role in CNS function or development is conceivable but has yet to be demonstrated. Thus, at this point, we cannot state whether ACY1 deficiency has pathogenic significance with pleiotropic clinical expression or is simply a biochemical variant. Awareness of this new genetic entity may help both in delineating its clinical significance and in avoiding erroneous diagnoses. 相似文献