全文获取类型
收费全文 | 941篇 |
免费 | 79篇 |
出版年
2024年 | 2篇 |
2023年 | 4篇 |
2022年 | 3篇 |
2021年 | 24篇 |
2020年 | 5篇 |
2019年 | 7篇 |
2018年 | 24篇 |
2017年 | 30篇 |
2016年 | 36篇 |
2015年 | 59篇 |
2014年 | 45篇 |
2013年 | 70篇 |
2012年 | 75篇 |
2011年 | 66篇 |
2010年 | 54篇 |
2009年 | 42篇 |
2008年 | 72篇 |
2007年 | 73篇 |
2006年 | 57篇 |
2005年 | 58篇 |
2004年 | 50篇 |
2003年 | 45篇 |
2002年 | 49篇 |
2001年 | 6篇 |
2000年 | 4篇 |
1999年 | 6篇 |
1998年 | 6篇 |
1997年 | 4篇 |
1996年 | 8篇 |
1995年 | 4篇 |
1994年 | 10篇 |
1993年 | 2篇 |
1992年 | 1篇 |
1991年 | 2篇 |
1990年 | 2篇 |
1988年 | 3篇 |
1987年 | 2篇 |
1986年 | 1篇 |
1985年 | 3篇 |
1983年 | 1篇 |
1982年 | 1篇 |
1977年 | 1篇 |
1975年 | 1篇 |
1974年 | 1篇 |
1968年 | 1篇 |
排序方式: 共有1020条查询结果,搜索用时 15 毫秒
71.
Coquelle N Fioravanti E Weik M Vellieux F Madern D 《Journal of molecular biology》2007,374(2):547-562
Lactate dehydrogenase (LDH) catalyzes the conversion of pyruvate to lactate with concomitant oxidation of NADH during the last step in anaerobic glycolysis. In the present study, we present a comparative biochemical and structural analysis of various LDHs adapted to function over a large temperature range. The enzymes were from Champsocephalus gunnari (an Antarctic fish), Deinococcus radiodurans (a mesophilic bacterium) and Thermus thermophilus (a hyperthermophilic bacterium). The thermodynamic activation parameters of these LDHs indicated that temperature adaptation from hot to cold conditions was due to a decrease in the activation enthalpy and an increase in activation entropy. The crystal structures of these LDHs have been solved. Pairwise comparisons at the structural level, between hyperthermophilic versus mesophilic LDHs and mesophilic versus psychrophilic LDHs, have revealed that temperature adaptation is due to a few amino acid substitutions that are localized in critical regions of the enzyme. These substitutions, each having accumulating effects, play a role in either the conformational stability or the local flexibility or in both. Going from hot- to cold-adapted LDHs, the various substitutions have decreased the number of ion pairs, reduced the size of ionic networks, created unfavorable interactions involving charged residues and induced strong local disorder. The analysis of the LDHs adapted to extreme temperatures shed light on how evolutionary processes shift the subtle balance between overall stability and flexibility of an enzyme. 相似文献
72.
73.
In the Bifrons to Aalensis Ammonite Zones of the Vrines section (Toarcian stratotype), woody phytoclasts, nonsaccate pollen grains, and marine assemblages (dinoflagellate cysts, acritarchs, and foraminiferal linings) dominate the palynofacies. The dinoflagellate cyst assemblage is cosmopolitan with minor Boreal influences, characterized by relatively high quantities of Micrhystridium, Baltisphaeridium, Mendicodinium spinosum, Nannoceratopsis, and the Parvocysta suite, dominating in turn the marine assemblages. Marine assemblage compositions, both dinoflagellate cysts and acritarchs, and calcareous nannofossil abundances are different in marl and limestone lithotypes of the Vrines section. Calcareous nannofossils are generally more abundant in marls than in limestones, they display however a cyclic pattern of semiquantitative abundances in phase with lithological cycles. Although a diagenetic overprint cannot be completely excluded to explain such a difference, it seems likely that these dissimilarities are in part primary, the results of variations in terms of proximality-distality, and climatic fluctuations. A mean duration of 117.6 Kyr per marl-limestone alternation, and the stacking of four marl-limestone alternations for 470.6 Kyr, suggest a control by the Earth's two orbital eccentricity cycles. It is likely that the palaeoenvironmental conditions, which influenced the formation of marl-limestone alternations, also controlled the variations in marine phytoplankton assemblages. 相似文献
74.
Franceschin M Alvino A Casagrande V Mauriello C Pascucci E Savino M Ortaggi G Bianco A 《Bioorganic & medicinal chemistry》2007,15(4):1848-1858
In developing G-quadruplex interactive telomerase inhibitors two main features have to be taken into account: the hydrophobic interactions with the G-quartet plane and the electrostatic interactions with the negatively charged phosphates of the four grooves. In this paper, we report the synthesis of four hydrosoluble coronene derivatives, which are characterized by a large hydrophobic aromatic core and four orthogonal hydrophilic side chains. We have studied their ability to induce both inter- and intramolecular G-quadruplex structures and found a significant selectivity of all the coronene derivatives for the intramolecular G-quadruplex. The efficiency in inhibiting human telomerase has been evaluated in a cell-free system and the experimental results correlate with the relative affinities of these compounds for the G-quadruplex monomeric structure, as derived by molecular modelling simulations. Thus, the coronene derivatives can be considered as a new class of telomerase inhibitors, although further investigations are surely necessary to fully exploit their features. 相似文献
75.
Debiaggi M Canducci F Terulla C Sampaolo M Marinozzi MC Alessandrino PE Colombo AA Caldera D Bragotti LZ Migliavacca R Bianchi E Romero E Clementi M 《The new microbiologica》2007,30(3):255-258
From October 2004 through October 2006 a study was performed to evaluate the prevalence of human Metapneumovirus (hMPV) infection in adult hematopoietic stem cell transplant (HSCT) recipients. Sequential nasopharyngeal aspirates (NPA) were collected independently from respiratory symptoms and evaluated for hMPV-RNA by polymerase chain reaction (PCR) and sequence analysis. Results indicate epidemiological and molecular differences between the 2004-2005 and 2005-2006 periods and that hMPV seems not to symptomatically affect HSCT patients or cause late respiratory sequelae. In addition, data collected suggest a hospital origin of hMPV infection in most HSCT patients during the 2004-2005 period. 相似文献
76.
Balbis E Patriarca S Furfaro AL Cottalasso D Pronzato MA Carlier P Botta F Marinari UM Fontana L Traverso N 《Redox report : communications in free radical research》2007,12(1):59-62
Results on oxidative markers during ageing are not consistent throughout the scientific literature; however, successful ageing may depend on better ability to cope with oxidative stress. A previous study of ours showed that successful ageing could actually be related to enhanced response to oxidatively modified proteins. In this study, a healthy nonagenarian population (OVER-90) was examined for various blood oxidative biomarkers and compared with a healthy population of blood donors (age range, 23-66 years). Blood glutathione, both total (tGSH) and oxidised (GSSG), and total plasmatic antioxidant status were maintained in the OVER-90 at a level similar to the control population. Sulphydryl (sulfhydryl) groups and glutathione peroxidase (GPx) were instead decreased. The results are discussed in a possible unifying view: the OVER-90 population could possess a globally preserved antioxidant ability, though some signs of oxidative damage are present and some structures could be 'sacrificed' in order to keep the redox equilibrium. 相似文献
77.
The 16S-23S rRNA gene internal transcribed spacer region (ITS1) from 34 strains of Pseudomonas avellanae and some strains of Pseudomonas syringae pathovars was amplified and assessed by restriction fragment length polymorphism (RFLP) using 10 restriction enzymes. In addition, the ITS1 region of four representative P. avellanae strains was sequenced and compared by the neighbour-joining algorithm with that of P. syringae pathovars. Two main groups of P. avellanae strains were observed that did not correlate with their origin. The ITS1 region sequencing revealed a high similarity with the P. syringae complex. One group of P. avellanae strains showed high similarity to P. s. pv. actinidiae and P. s. pv. tomato; another group showed similarity with P. s. pv. tabaci and P. s. pv. glycinea. Two strains clustered with P. s. pv. pisi. The difficulties to unambiguously classify the strains associated with hazelnut decline in Greece and Italy are discussed. 相似文献
78.
The TBF-1 is an 11.9-kDa fruiting body specific protein of the Ascomycetes hypogeous fungus Tuber borchii Vittad. found in aqueous extract and the hyphal cell wall. The tbf-1 gene codes a 12-amino acid N-terminal stretch not present in mature protein. This sequence does not match with any homologous signal sequences stored in data banks. To investigate the role of the N-terminus in TBF-1 localization, cDNA was expressed in Saccharomyces cerevisiae under the control of the 3-phosphoglycerate kinase promoter. Like Tuber, yeast also produces and secretes TBF-1 and the foreign protein binds with the cell wall. A signalless mutant protein was constructed; this DeltaTBF-1 was expressed but not exported by yeast. The secretion of TBF-1 was also suppressed using the sec18(ts) yeast mutant strain grown at nonpermissive temperature as host. Thus we demonstrated that the N-terminal 12-amino acid stretch is a noncanonical signal peptide that leads the TBF-1 toward the classical secretory pathway in yeast. 相似文献
79.
In the present study, we used tumor necrosis factor-R1 knock out mice (TNF-αR1KO) to understand the roles of TNF-α on epithelial function in models of carrageenan-induced acute lung inflammation. In order to elucidate whether the observed anti-inflammatory status is related to the inhibition of TNF-α, we also investigated the effect of etanercept, a TNF-α soluble receptor construct, on lung TJ function. Pharmacological and genetic TNF-α inhibition significantly reduced the degree of (1) TNF-α production in pleural exudates and in the lung tissues, (2) the inflammatory cell infiltration in the pleural cavity as well as in the lung tissues (evaluated by MPO activity), (3) the alteration of ZO-1, Claudin-2, Claudin-4, Claudin-5 and β-catenin (immunohistochemistry) and (4) apoptosis (TUNEL staining, Bax, Bcl-2 expression). Taken together, our results demonstrate that inhibition of TNF-α reduces the tight junction permeability in the lung tissues associated with acute lung inflammation, suggesting a possible role of TNF-α on lung barrier dysfunction. 相似文献
80.