全文获取类型
收费全文 | 3294篇 |
免费 | 230篇 |
专业分类
3524篇 |
出版年
2021年 | 22篇 |
2020年 | 28篇 |
2019年 | 22篇 |
2018年 | 40篇 |
2017年 | 36篇 |
2016年 | 51篇 |
2015年 | 95篇 |
2014年 | 122篇 |
2013年 | 173篇 |
2012年 | 162篇 |
2011年 | 175篇 |
2010年 | 101篇 |
2009年 | 94篇 |
2008年 | 153篇 |
2007年 | 200篇 |
2006年 | 178篇 |
2005年 | 170篇 |
2004年 | 161篇 |
2003年 | 149篇 |
2002年 | 143篇 |
2001年 | 45篇 |
2000年 | 31篇 |
1999年 | 38篇 |
1998年 | 37篇 |
1997年 | 40篇 |
1996年 | 35篇 |
1995年 | 37篇 |
1994年 | 29篇 |
1993年 | 41篇 |
1992年 | 24篇 |
1991年 | 25篇 |
1990年 | 29篇 |
1989年 | 33篇 |
1988年 | 41篇 |
1987年 | 33篇 |
1986年 | 22篇 |
1985年 | 32篇 |
1984年 | 27篇 |
1983年 | 42篇 |
1982年 | 38篇 |
1981年 | 36篇 |
1980年 | 40篇 |
1979年 | 30篇 |
1978年 | 33篇 |
1977年 | 28篇 |
1976年 | 24篇 |
1975年 | 25篇 |
1973年 | 26篇 |
1970年 | 21篇 |
1967年 | 18篇 |
排序方式: 共有3524条查询结果,搜索用时 0 毫秒
231.
Schröder H Elosua R Vila J Marti H Covas MI Marrugat J 《Obesity (Silver Spring, Md.)》2007,15(3):557-562
Objective: To evaluate time trends of obesity, abdominal obesity, and cardiovascular risk factors (CRFs) according to BMI and waist circumference (WC) categories in a Mediterranean population. Research Methods and Procedures: Subjects were Spanish men (n = 2383) and women (n = 2525) 25 to 74 years old, examined in 1994 to 1995 and 1999 to 2000 in two independent population‐based cross‐sectional surveys in the northeast of Spain. Lifestyle measures, CRFs, and anthropometric variables were analyzed. Results: Over the 5 years of the study, mean age‐standardized BMI increased by 1.0 units in men and by 0.8 units in women. At the same time the prevalence of obesity increased from 15.4% to 21.9% in men and from 15.4% to 21.4% in women. An upward trend was observed for WC and abdominal obesity (WC > 102 cm in men and WC > 88 cm in women) only in men. The proportion of men and women with hypercholesterolemia, diabetes, and low high‐density lipoprotein‐cholesterol plasma concentration remained stable within BMI and WC categories. The proportion of hypertension and smoking in obese men significantly increased from 1995 to 2000. Discussion: The 5‐year increase in BMI and WC is of considerable magnitude in the present population, although several CRFs remained stable within BMI and WC categories. 相似文献
232.
Jentsch W Schweigel M Weissbach F Scholze H Pitroff W Derno M 《Archives of animal nutrition》2007,61(1):10-19
In this study data originating from complete metabolic trials with cattle of both sexes, fed 337 rations at feed intake levels between one to three times maintenance energy requirement were used to regress the total CH4 emission to the level of DM intake and to the nutrient composition, respectively. A major component of the measured CH4 emission cannot be explained by DM intake but is rather due to differences in dietary nutrient composition. The amount of digestible nutrients especially of the carbohydrate fraction (starch, sugar, N-free residuals) are reliable to estimate CH4 release with high precision (r2 = 0.885). Its production rate increased to 1.9-fold higher levels (range 1.8-2.1) per g of N-free residuals compared to that induced per g of protein, starch or sugar, respectively. Furthermore, diets rich in fat reduced CH4 formation in the rumen. The regression equations fit a wide range of diets and diet compositions, and more importantly, they are applicable to various types of production systems. 相似文献
233.
Comparative quantitative proteomics to investigate the remodeling of bioenergetic pathways under iron deficiency in Chlamydomonas reinhardtii 总被引:2,自引:0,他引:2
Naumann B Busch A Allmer J Ostendorf E Zeller M Kirchhoff H Hippler M 《Proteomics》2007,7(21):3964-3979
The basic question addressed in this study is how energy metabolism is adjusted to cope with iron deficiency in Chlamydomonas reinhardtii. To investigate the impact of iron deficiency on bioenergetic pathways, comparative proteomics was combined with spectroscopic as well as voltametric oxygen measurements to assess protein dynamics linked to functional properties of respiratory and photosynthetic machineries. Although photosynthetic electron transfer is largely compromised under iron deficiency, our quantitative and spectroscopic data revealed that the functional antenna size of photosystem II (PSII) significantly increased. Concomitantly, stress-related chloroplast polypeptides, like 2-cys peroxiredoxin and a stress-inducible light-harvesting protein, LhcSR3, as well as a novel light-harvesting protein and several proteins of unknown function were induced under iron-deprivation. Respiratory oxygen consumption did not decrease and accordingly, polypeptides of respiratory complexes, harboring numerous iron-sulfur clusters, were only slightly diminished or even increased under low iron. Consequently, iron-deprivation induces a transition from photoheterotrophic to primarily heterotrophic metabolism, indicating that a hierarchy for iron allocations within organelles of a single cell exists that is closely linked with the metabolic state of the cell. 相似文献
234.
In a comparative proteome analysis of peripheral blood mononuclear cells (PBMCs), we analyzed 130 two-dimensional gels obtained from 33 healthy control individuals and 32 patients diagnosed with rheumatoid arthritis (RA). We found 16 protein spots that are deregulated in patients with RA and, using peptide mass fingerprinting and Western blot analyses, identified these spots as belonging to 9 distinct proteins. A hierarchical clustering procedure organizes the study subjects into two main clusters based on the expression of these 16 protein spots, one that contains mostly healthy control individuals and the other mostly RA patients. The majority of the proteins differentially expressed in RA patients when compared with healthy controls can be detected as protein fragments in PBMCs obtained from RA patients. This set of deregulated proteins includes several factors that have been shown to be autoantigens in autoimmune diseases. 相似文献
235.
Folding of VemP into translation-arresting secondary structure is driven by the ribosome exit tunnel
Michal H Kol Gabor Nagy John Kunkel Sara M Vaiana Lars V Bock Helmut Grubmüller 《Nucleic acids research》2022,50(4):2258
The ribosome is a fundamental biomolecular complex that synthesizes proteins in cells. Nascent proteins emerge from the ribosome through a tunnel, where they may interact with the tunnel walls or small molecules such as antibiotics. These interactions can cause translational arrest with notable physiological consequences. Here, we studied the arrest caused by the regulatory peptide VemP, which is known to form α-helices inside the ribosome tunnel near the peptidyl transferase center under specific conditions. We used all-atom molecular dynamics simulations of the entire ribosome and circular dichroism spectroscopy to study the driving forces of helix formation and how VemP causes the translational arrest. To that aim, we compared VemP dynamics in the ribosome tunnel with its dynamics in solution. We show that the VemP peptide has a low helical propensity in water and that the propensity is higher in mixtures of water and trifluorethanol. We propose that helix formation within the ribosome is driven by the interactions of VemP with the tunnel and that a part of VemP acts as an anchor. This anchor might slow down VemP progression through the tunnel enabling α-helix formation, which causes the elongation arrest. 相似文献
236.
Manuela G. Neuman Helmut K. Seitz Rolf Teschke Stephen Malnick Kamisha L. Johnson-Davis Lawrence B. Cohen Anit German Nicolas Hohmann Bernhardo Moreira George Moussa Mihai Opris 《Current issues in molecular biology》2022,44(3):1294
Hepatic cells are sensitive to internal and external signals. Ethanol is one of the oldest and most widely used drugs in the world. The focus on the mechanistic engine of the alcohol-induced injury has been in the liver, which is responsible for the pathways of alcohol metabolism. Ethanol undergoes a phase I type of reaction, mainly catalyzed by the cytoplasmic enzyme, alcohol dehydrogenase (ADH), and by the microsomal ethanol-oxidizing system (MEOS). Reactive oxygen species (ROS) generated by cytochrome (CYP) 2E1 activity and MEOS contribute to ethanol-induced toxicity. We aimed to: (1) Describe the cellular, pathophysiological and clinical effects of alcohol misuse on the liver; (2) Select the biomarkers and analytical methods utilized by the clinical laboratory to assess alcohol exposure; (3) Provide therapeutic ideas to prevent/reduce alcohol-induced liver injury; (4) Provide up-to-date knowledge regarding the Corona virus and its affect on the liver; (5) Link rare diseases with alcohol consumption. The current review contributes to risk identification of patients with alcoholic, as well as non-alcoholic, liver disease and metabolic syndrome. Additional prevalence of ethnic, genetic, and viral vulnerabilities are presented. 相似文献
237.
The Salmonella SpiC protein targets the mammalian Hook3 protein function to alter cellular trafficking 总被引:4,自引:0,他引:4
The Salmonella SpiC protein is secreted into the cytosol of macrophages via a unique type III secretion system that functions intracellularly to translocate proteins across the phagosomal membrane. The SpiC protein is required for survival within macrophages and inhibition of phagosome-lysosome fusion in vivo, and it is sufficient to inhibit endosome-endosome fusion in vitro. Here, we establish that SpiC targets the function of Hook3, a mammalian protein implicated in cellular trafficking. Purified GST-SpiC pulled down Hook3 from murine macrophages, and anti-Hook3 antibodies precipitated SpiC from the cytosol of Salmonella-infected macrophages. Expression of the spiC gene disrupted Golgi morphology in Vero cells and altered the distribution of lysosomes in macrophages, mimicking the phenotype of cells expressing a hook3 dominant-negative mutant. By inactivating Hook3 function, the SpiC protein may alter the lysosome network and prevent phagosome-lysosome fusion. 相似文献
238.
The nature of replication origins in eukaryotic chromosomes has been examined in some detail only in yeast, Drosophila, and mammalian cells. We have used highly synchronous cultures of plasmodia of the myxomycete Physarum and two-dimensional agarose gel electrophoresis to examine replication of two developmentally controlled, early replicated genes over time in S-phase. A single, discrete origin of replication was found within 4.8 kb of the LAV1-5 gene, which encodes a homolog of profilin. In contrast, the LAV1-2 gene appears to be surrounded by several origins. Two origins were identified within a 15 kb chromosomal domain and appear to be inefficiently used. Replication forks collide at preferred sites within this domain. These terminating structures are long lived, persisting for at least 2 h of the 3 h S-phase. Analysis of restriction fragment length polymorphisms (RFLPs) within the LAV1-2 domain indicates that replication of alleles on different parental chromosomes is a highly coordinated process. Our studies of the these two early replicated, plasmodium-specific genes indicate that both a fixed, narrow origin region and a broader zone containing two closely spaced origins of DNA replication occur in Physarum. 相似文献
239.
Anna Swierzko Lore Brade Elisabeth C. Höffgen Helmut Brade 《FEMS immunology and medical microbiology》1993,7(3):265-270
Abstract Rabbit polyclonal antibodies against the lipopolysaccharide (LPS) of the Rd1 P− mutant strain R7 of Salmonella minnesota were serologically characterized using R7 LPS, dephosphorylated LPS, deacylated LPS, deacylated, dephosphorylated and reduced LPS, and synthetic partial structures. The latter comprised partial structures of the core region of Rd1 P− LPS bound to the β 1 → 6-linked glucosamine disaccharide with two amide-linked 3-hydroxytetradecanoic acid residues or artificial glycoconjugates comprised of the synthetic oligosaccharides coupled to bovine serum albumin. Using a passive hemolysis and an enzyme immunoassay, absorption and inhibition experiments, the antibody specificities present could be determined. One group of antibodies required components of the core region and the phosphorylated glucosamine disaccharide of the lipid A moiety for binding. The majority of phosphate-independent antibodies was directed against the trisaccharide l -glycero-α- d -manno-heptopyranose(1 → 3)- l -glycero-α- d -manno-heptopyranose(1 → 5)3-deoxy- d -manno-octulosonic acid. Antibodies against the 1 → 3- and 1 → 7-linked heptose disaccharides and against a single heptose were also detected, however, with low titers. No antibodies were found which required the presence of fatty acids. 相似文献
240.
Marko D. Mihovilovic Bernhard Müller Margaret M. Kayser Jon D. Stewart Johannes Frhlich Peter Stanetty Helmut Spreitzer 《Journal of Molecular Catalysis .B, Enzymatic》2001,11(4-6):349-353
Whole cells of an Escherichia coli strain overexpressing Acinetobacter sp. NCIB 9871 cyclohexanone monooxygenase (CHMO; E.C. 1.14.13.22) have been used for the Baeyer-Villiger oxidation of representative heterocyclic six-membered ketones to probe the potential impact of nitrogen, sulfur and oxygen on the chemoselectivity of these reactions. The fact that all of these heterocyclic systems were accepted as substrates by the enzyme and gave normal Baeyer-Villiger products broadens the synthetic utility of the engineered E. coli strain and emphasizes the chemoselectivity achievable with enzymatic oxidation catalysts. 相似文献