全文获取类型
收费全文 | 624篇 |
免费 | 84篇 |
专业分类
708篇 |
出版年
2022年 | 4篇 |
2021年 | 12篇 |
2020年 | 6篇 |
2019年 | 6篇 |
2018年 | 14篇 |
2017年 | 8篇 |
2016年 | 11篇 |
2015年 | 28篇 |
2014年 | 22篇 |
2013年 | 31篇 |
2012年 | 37篇 |
2011年 | 47篇 |
2010年 | 20篇 |
2009年 | 26篇 |
2008年 | 35篇 |
2007年 | 28篇 |
2006年 | 28篇 |
2005年 | 32篇 |
2004年 | 32篇 |
2003年 | 23篇 |
2002年 | 13篇 |
2001年 | 13篇 |
2000年 | 14篇 |
1999年 | 23篇 |
1998年 | 9篇 |
1997年 | 6篇 |
1996年 | 10篇 |
1995年 | 9篇 |
1994年 | 8篇 |
1993年 | 5篇 |
1992年 | 8篇 |
1991年 | 11篇 |
1990年 | 7篇 |
1988年 | 4篇 |
1987年 | 5篇 |
1986年 | 7篇 |
1985年 | 4篇 |
1984年 | 5篇 |
1983年 | 8篇 |
1982年 | 13篇 |
1980年 | 5篇 |
1979年 | 7篇 |
1977年 | 3篇 |
1974年 | 3篇 |
1973年 | 6篇 |
1971年 | 7篇 |
1970年 | 3篇 |
1969年 | 3篇 |
1966年 | 4篇 |
1956年 | 3篇 |
排序方式: 共有708条查询结果,搜索用时 15 毫秒
61.
Damage caused to Saccharomyces cerevisiae SY4 plasma membrane H(+)-ATPase by Fe- and Cu-Fenton reagents was determined in secretory vesicles containing enzyme in which Cys residues were replaced singly or in pairs by Ala. Cys-221 situated in a beta-sheet domain between M2 and M3 segments, phosphorylation domain-located Cys-409 and Cys-532 situated at the ATP-binding site play a role in the inactivation. In the presence of all three residues the enzyme exhibited a certain basic inactivation, which did not change when Cys-532 was replaced with Ala. In mutants having intact Cys-532 but lacking one or both other cysteines, replacement of Cys-221 with Ala led to lower inactivation, suggesting that Cys-221 may serve as a target for metal-catalyzed oxidation and intact Cys-532 promotes this target role of Cys-221. In contrast, the absence of Cys-409 caused higher inactivation by Fe-Fenton. Cys-532 thus seems to serve as a target for Fe-Fenton, intact Cys-409 causing a conformational change that makes Cys-532 less accessible to oxidation. The mutant lacking both Cys-221 and Cys-409 is more sensitive to Fe-Fenton than to Cu-Fenton and the absence of both Cys residues thus seems to expose presumable extra Fe-binding sites. These data and those on protection by ATP, ADP, 1,4-dithiothreitol and deferrioxamine B point to complex interactions between individual parts of the enzyme molecule that determine its sensitivity towards Fenton reagents. ATPase fragmentation caused by the two reagents differed in that the Fe-Fenton reagent produced in Western blot "smears" whereas the Cu-Fenton reagent produced defined fragments. 相似文献
62.
Stadler K Masignani V Eickmann M Becker S Abrignani S Klenk HD Rappuoli R 《Nature reviews. Microbiology》2003,1(3):209-218
The 114-day epidemic of the severe acute respiratory syndrome (SARS) swept 29 countries, affected a reported 8,098 people, left 774 patients dead and almost paralyzed the Asian economy. Aggressive quarantine measures, possibly aided by rising summer temperatures, successfully terminated the first eruption of SARS and provided at least a temporal break, which allows us to consolidate what we have learned so far and plan for the future. Here, we review the genomics of the SARS coronavirus (SARS-CoV), its phylogeny, antigenic structure, immune response and potential therapeutic interventions should the SARS epidemic flare up again. 相似文献
63.
Pilot study of elevated levels of insulin-like growth factor-binding protein-2 as indicators of hepatocellular carcinoma 总被引:3,自引:0,他引:3
Ranke MB Maier KP Schweizer R Stadler B Schleicher S Elmlinger MW Flehmig B 《Hormone research》2003,60(4):174-180
BACKGROUND/AIMS: Insulin-like growth factor-binding protein-2 (IGFBP-2) is expressed in many malignant tissues, and elevated serum levels can be indicators of tumour activity in addition to conventional tumour markers. Our aim was to evaluate the role of IGFBP-2 levels together with insulin-like growth factor (IGF)-I, IGF-II and IGFBP-3 in the diagnostic work-up of patients with hepatocellular carcinoma (HCC). METHODS: In 50 (39 males, 11 females) histologically confirmed and TNM-graded patients with HCC who had not received adjuvant chemotherapy, the basal serum levels of IGF-I, IGF-II, IGFBP-3, IGFBP-2 and alpha-fetoprotein (AFP) were measured. The median age of the patients was 66 (37-84) years, body mass index was normal (25 (35-16) kg/m2). RESULTS: The levels of IGF-I, IGF-II and IGFBP-3 were diminished, as is the case when nutrition, hepatic function and growth hormone (GH) secretion are decreased. The levels of AFP and IGFBP-2 were markedly high. In 37 cases, IGFBP-2 levels were above the age-related norm, and in 40 cases AFP levels were also elevated. In 3 cases, both AFP and IGFBP-3 were normal, and in 4 cases AFP was high but IGFBP-2 normal, whereas in 10 cases AFP was normal but IGFBP-2 was high. CONCLUSIONS: In addition to AFP, IGFBP-2 appears to be a suitable marker for the evaluation of the serological status of HCC patients. A longitudinal study during disease management is required to assess the full potential of IGFBP-2 measurements as a marker. 相似文献
64.
In the absence of added Fe2+, the ATPase activity of isolatedSchizosaccharomyces pombe plasma membranes (5–7 μmolP
i per mg protein per min) is moderately inhibited by H2O2 in a concentration-dependent manner. Sizable inactivation occurs only at 50–80 mmol/L H2O2. The process, probably a direct oxidative action of H2O2 on the enzyme, is not induced by the indigenous membrane-bound iron (19.3 nmol/mg membrane protein), is not affected by the
radical scavengers mannitol and Tris, and involves a decrease of both theK
m of the enzyme for ATP and theV of ATP splitting. On exposing the membranes to the Fenton reagent (50 μmol/L Fe2+ +20 mmol/L H2O2), which causes a fast production of HO− radicals, the ATPase is 50–60% inactivated and 90% of added Fe2+ is oxidized to Fe3+ within 1 min. The inactivation occurs only when Fe2+ is added before H2O2 and can thus bind to the membranes. The lack of effect of radical scavengers (mannitol, Tris) indicates that HO− radicals produced in the bulk phase play no role in inactivation. Blockage of the inactivation by the iron chelator deferrioxamine
implies that the process requires the presence of Fe2+ ions bound to binding sites on the enzyme molecules. Added catalase, which competes with Fe2+ for H2O2, slows down the inactivation but in some cases increases its total extent, probably due to the formation of the superoxide
radical that gives rise to delayed HO− production. 相似文献
65.
Peter R. Wills Stuart A. Kauffman Barbel M. R. Stadler Peter F. Stadler 《Bulletin of mathematical biology》1998,60(6):1073-1098
The theory of autocatalytic binary ligation is reviewed within the context of a consistently applied Michaelis-Menten quasi-steady-state
approximation to obtain explicit analytical results describing time-course data from experiments. A detailed protocol for
the step-wise elucidation of a minimal set of experimental parameters is outlined. The kinetic equations are then generalized
to cases of self-and cross-catalysis among an arbitrary number of different templates and applied to experiments involving
just two templates. Depending on the values of various kinetic parameters such systems can display exclusionary Darwinian
selection corresponding to an exponential growth law, selective coexistence or coexistence of all species characteristic of
a parabolic growth law; the intermediate behaviour arises as a property of the full mechanism analysed here. Our results are
applicable to the classical case of self-replicating nucleic acids and their analogues as well as to newly discovered self-replicating
peptides. 相似文献
66.
Luo J Stadler PF He S Meyer A 《Journal of experimental zoology. Part B. Molecular and developmental evolution》2007,308(3):250-258
A tetraploidization event took place in the cyprinid lineage leading to goldfishes about 15 million years ago. A PCR survey for Hox genes in the goldfish Carassius auratus auratus (Actinopterygii: Cyprinidae) was performed to assess the consequences of this genome duplication. Not surprisingly, the genomic organization of the Hox gene clusters of goldfish is similar to that of the closely related zebrafish (Danio rerio). However, the goldfish exhibits a much larger number of recent pseudogenes, which are characterized by indels. These findings are consistent with the hypothesis that dosage effects cause selection pressure to rapidly silence crucial developmental regulators after a tetraploidization event. 相似文献
67.
Fungi are key players in terrestrial ecosystem functions. They are not only indispensable symbionts of most of the terrestrial plants, but can also interact with almost all organisms and are the major decomposers of organic matter. Indeed, they are involved in most ecosystem services, so much that life on earth would not have evolved without them. Competition among fungi and with other organism groups has driven evolution of offensive and defensive mechanisms, including the production of secondary metabolites, which continue to be widely unexplored. In addition, fungal plant parasites threaten the global agricultural production and are therefore of highest relevance for human health and survival. Given the ecological and economical relevance of fungi, advancement of other biological and physical sciences are impeded because mycology—the science devoted to the study of fungi—is insufficiently recognized as a major field of life science and supported in basic and applied research and economic contexts. 相似文献
68.
Niehuis O Hartig G Grath S Pohl H Lehmann J Tafer H Donath A Krauss V Eisenhardt C Hertel J Petersen M Mayer C Meusemann K Peters RS Stadler PF Beutel RG Bornberg-Bauer E McKenna DD Misof B 《Current biology : CB》2012,22(14):1309-1313
The phylogeny of insects, one of the most spectacular radiations of life on earth, has received considerable attention. However, the evolutionary roots of one intriguing group of insects, the twisted-wing parasites (Strepsiptera), remain unclear despite centuries of study and debate. Strepsiptera exhibit exceptional larval developmental features, consistent with a predicted step from direct (hemimetabolous) larval development to complete metamorphosis that could have set the stage for the spectacular radiation of metamorphic (holometabolous) insects. Here we report the sequencing of a Strepsiptera genome and show that the analysis of sequence-based genomic data (comprising more than 18 million nucleotides from nearly 4,500 genes obtained from a total of 13 insect genomes), along with genomic metacharacters, clarifies the phylogenetic origin of Strepsiptera and sheds light on the evolution of holometabolous insect development. Our results provide overwhelming support for Strepsiptera as the closest living relatives of beetles (Coleoptera). They demonstrate that the larval developmental features of Strepsiptera, reminiscent of those of hemimetabolous insects, are the result of convergence. Our analyses solve the long-standing enigma of the evolutionary roots of Strepsiptera and reveal that the holometabolous mode of insect development is more malleable than previously thought. 相似文献
69.