全文获取类型
收费全文 | 612篇 |
免费 | 74篇 |
国内免费 | 1篇 |
出版年
2023年 | 5篇 |
2022年 | 9篇 |
2021年 | 23篇 |
2020年 | 10篇 |
2019年 | 9篇 |
2018年 | 13篇 |
2017年 | 14篇 |
2016年 | 18篇 |
2015年 | 24篇 |
2014年 | 31篇 |
2013年 | 48篇 |
2012年 | 45篇 |
2011年 | 58篇 |
2010年 | 30篇 |
2009年 | 28篇 |
2008年 | 25篇 |
2007年 | 38篇 |
2006年 | 34篇 |
2005年 | 18篇 |
2004年 | 10篇 |
2003年 | 16篇 |
2002年 | 13篇 |
2001年 | 11篇 |
2000年 | 14篇 |
1999年 | 8篇 |
1998年 | 7篇 |
1997年 | 5篇 |
1996年 | 5篇 |
1992年 | 8篇 |
1991年 | 8篇 |
1990年 | 6篇 |
1989年 | 7篇 |
1988年 | 8篇 |
1987年 | 6篇 |
1986年 | 3篇 |
1985年 | 6篇 |
1983年 | 5篇 |
1982年 | 4篇 |
1981年 | 4篇 |
1980年 | 4篇 |
1979年 | 4篇 |
1978年 | 7篇 |
1977年 | 3篇 |
1976年 | 3篇 |
1974年 | 3篇 |
1973年 | 3篇 |
1972年 | 4篇 |
1971年 | 3篇 |
1969年 | 6篇 |
1968年 | 3篇 |
排序方式: 共有687条查询结果,搜索用时 156 毫秒
31.
Sunita Panda Ananya Nanda Nilanjan Sahu Deepak K. Ojha Biswaranjan Pradhan Anjali Rai Amol
R. Suryawanshi Nilesh Banavali Sasmita Nayak 《Bioscience reports》2022,42(3)
Inteins are auto-processing domains that implement a multistep biochemical reaction termed protein splicing, marked by cleavage and formation of peptide bonds. They excise from a precursor protein, generating a functional protein via covalent bonding of flanking exteins. We report the kinetic study of splicing and cleavage reaction in [Fe–S] cluster assembly protein SufB from Mycobacterium tuberculosis (Mtu). Although it follows a canonical intein splicing pathway, distinct features are added by extein residues present in the active site. Sequence analysis identified two conserved histidines in the N-extein region; His-5 and His-38. Kinetic analyses of His-5Ala and His-38Ala SufB mutants exhibited significant reductions in splicing and cleavage rates relative to the SufB wildtype (WT) precursor protein. Structural analysis and molecular dynamics (MD) simulations suggested that Mtu SufB displays a unique mechanism where two remote histidines work concurrently to facilitate N-terminal cleavage reaction. His-38 is stabilized by the solvent-exposed His-5, and can impact N–S acyl shift by direct interaction with the catalytic Cys1. Development of inteins as biotechnological tools or as pathogen-specific novel antimicrobial targets requires a more complete understanding of such unexpected roles of conserved extein residues in protein splicing. 相似文献
32.
Oral pathogens have created a menace in recent years due to biofilm formation and antimicrobial drug resistance. The current treatment strategy works well with antibiotics. However, constant use of antibiotics creates a selective pressure, which increases adaptability of the pathogens. Therefore, it is of interest to analyze the potential targets of genistein in dental pathogens using computer aided prediction tools. 相似文献
33.
Pathological alterations in various organs of rohu (L. rohita) fingerlings following acute (0, 7.50, 11.25 and 13.75 mg/kg body weight) and subchronic (0, 1.25 and 2.50 mg/kg body weight) single i.p. aflatoxin B1 exposure for 10 and 90 days, respectively, were investigated. Mortality (dose-dependent) was marked only during acute toxicosis. The changes observed in various organs were dose and time dependent. The acute dose groups revealed toxic changes viz., necrotic and vascular changes in liver and gill lamellae; meningitis, congestion in brain, degeneration and inflammatory reaction in heart along with degenerative to necrotic changes in kidney tubules and sloughing of the intestinal mucosa. During subchronic exposure to this toxin, preneoplastic lesions in liver along with changes in spleen, intestine, gill and pancreas were recorded. With low doses of aflatoxin, the fish did not reveal any mortality or external signs other than catchexia and increased pigmentation on scales. In composite culture practice of Indian major carps, this could be of economic significance. 相似文献
34.
We have prepared a mutant RecA protein in which proline 67 and glutamic acid 68 in the NTP binding site were replaced by a glycine and alanine residue, respectively. The [P67G/E68A]RecA protein catalyzes the single-stranded DNA-dependent hydrolysis of ATP and is able to promote the standard ATP-dependent three-strand exchange reaction between a circular bacteriophage phiX174 (phiX) single-stranded DNA molecule and a homologous linear phiX double-stranded (ds) DNA molecule (5.4 kilobase pairs). The strand exchange activity differs from that of the wild type RecA protein, however, in that it is (i) completely inhibited by an ATP regeneration system, and (ii) strongly stimulated by the addition of high concentrations of ADP to the reaction solution. These results indicate that the strand exchange activity of the [P67G/E68A]RecA protein is dependent on the presence of both ATP and ADP. The ADP dependence of the reaction is reduced or eliminated when (i) a shorter linear phiX dsDNA fragment (1.1 kilobase pairs) is substituted for the full-length linear phiX dsDNA substrate, or (ii) the Mg(2+) concentration is reduced to a level just sufficient to complex the ATP present in the reaction solution. These results indicate that it is the branch migration phase (and not the initial pairing step) of the [P67G/E68A]RecA protein-promoted strand exchange reaction that is dependent on ADP. It is likely that the [P67G/E68A]RecA mutation has revealed a requirement for ADP that also exists (but is not as readily apparent) in the strand exchange reaction of the wild type RecA protein. 相似文献
35.
Retinyl esters (RE) have been used extensively as markers to study chylomicron (CM) catabolism because they are secreted in the postprandial state with CM and do not exchange with other lipoproteins in the plasma. To understand the mechanism of secretion of RE by the intestine under the fasting and postprandial states, differentiated Caco-2 cells were supplemented with radiolabeled retinol under conditions that support or do not support CM secretion. We observed that these cells assimilate vitamin A by a rapid uptake mechanism. After uptake, cells store retinol in both esterified and unesterified forms. Under fasting conditions, cells do not secrete RE but secrete free retinol unassociated with lipoproteins. Under postprandial conditions, cells secrete significant amounts of RE only with CM. The secretion of RE with CM was independent of the rate of uptake of retinol and intracellular free and esterified retinol levels, and was absolutely dependent on the assembly and secretion of CM. The secretion of RE was correlated with the secretion of CM and not with the secretion of total apolipoprotein B. Inhibition of CM secretion by Pluronic L81 decreased the secretion of RE and did not result in their increased secretion with smaller lipoproteins. These data strongly suggest that RE secretion by the intestinal cells is a specific and regulated process that occurs in the postprandial state and is dependent on the assembly and secretion of CM. We propose that RE are added to CM during final stages of lipoprotein assembly and may serve as signposts for these steps. 相似文献
36.
The immunosuppressive effects of bath exposure to a sub lethal concentration of the synthetic pyrethroid alpha-permethrin (3.05 x 10(-4) mg l(-1)) in the Indian Major carp, Labeo rohita was studied after 45 days' exposure. In some groups, the effects of alpha-permethrin on non-specific defences and serum enzymes of carp were investigated after challenge with Aeromonas hydrophila. Several nonspecific immune responses and serum enzymes were reduced after exposure of alpha-permethrin. Bactericidal activity of rohu serum was reduced significantly in pesticide and bacteria treated fish. The Glutamic Oxaloacetate Transaminase (GOT) and Glutamic Pyruvate Transaminase (GPT) activity were increased in immunosuppressed fish. Blood glucose level was elevated significantly and Hb% was reduced significantly in pesticide and bacteria treated fishes as compared to the negative control. 相似文献
37.
The mismatch repair proteins, MutS and MutL, interact in a DNA mismatch and ATP-dependent manner to activate downstream events in repair. Here, we assess the role of ATP binding and hydrolysis in mismatch recognition by MutS and the formation of a ternary complex involving MutS and MutL bound to a mismatched DNA. We show that ATP reduces the affinity of MutS for mismatched DNA and that the modulation of DNA binding affinity by nucleotide is even more pronounced for MutS E694A, a protein that binds ATP but is defective for ATP hydrolysis. Despite the ATP hydrolysis defect, E694A, like WT MutS, undergoes rapid, ATP-dependent dissociation from a DNA mismatch. Furthermore, MutS E694A retains the ability to interact with MutL on mismatched DNA. The recruitment of MutL to a mismatched DNA by MutS is also observed for two mutant MutL proteins, E29A, defective for ATP hydrolysis, and R266A, defective for DNA binding. These results suggest that ATP binding in the absence of hydrolysis is sufficient to trigger formation of a MutS sliding clamp. However, recruitment of MutL results in the formation of a dynamic ternary complex that we propose is the intermediate that signals subsequent repair steps requiring ATP hydrolysis. 相似文献
38.
Basic residues of the helix six domain of influenza virus M1 involved in nuclear translocation of M1 can be replaced by PTAP and YPDL late assembly domain motifs
下载免费PDF全文
![点击此处可从《Journal of virology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Influenza type A virus matrix (M1) protein possesses multiple functional motifs in the helix 6 (H6) domain (amino acids 91 to 105), including nuclear localization signal (NLS) (101-RKLKR-105) involved in translocating M1 from the cytoplasm into the nucleus. To determine the role of the NLS motif in the influenza virus life cycle, we mutated these and the neighboring sequences by site-directed mutagenesis, and influenza virus mutants were generated by reverse genetics. Our results show that infectious viruses were rescued by reverse genetics from all single alanine mutations of amino acids in the H6 domain and the neighboring region except in three positions (K104A and R105A within the NLS motif and E106A in loop 6 outside the NLS motif). Among the rescued mutant viruses, R101A and R105K exhibited reduced growth and small-plaque morphology, and all other mutant viruses showed the wild-type phenotype. On the other hand, three single mutations (K104A, K105A, and E106A) and three double mutations (R101A/K102A, K104A/K105A, and K102A/R105A) failed to generate infectious virus. Deletion (Delta YRKL) or mutation (4A) of YRKL also abolished generation of infectious virus. However, replacement of the YRKL motif with PTAP or YPDL as well as insertion of PTAP after 4A mutation yielded infectious viruses with the wild-type phenotype. Furthermore, mutant M1 proteins (R101A/K102A, Delta YRKL, 4A, PTAP, 4A+PTAP, and YPDL) when expressed alone from cloned cDNAs were only cytoplasmic, whereas the wild-type M1 expressed alone was both nuclear and cytoplasmic as expected. These results show that the nuclear translocation function provided by the positively charged residues within the NLS motif does not play a critical role in influenza virus replication. Furthermore, these sequences of H6 domain can be replaced by late (L) domain motifs and therefore may provide a function similar to that of the L domains of other negative-strand RNA and retroviruses. 相似文献
39.
Synergized bifenthrin plus chlorpyrifos-methyl for control of beetles and psocids in sorghum in Australia 总被引:1,自引:0,他引:1
The efficacy of bifenthrin (0.5 mg/kg) + piperonyl butoxide (7 mg/kg) + chlorpyrifosmethyl (10 mg/kg) against beetle and psocid pests of sorghum was evaluated in silo-scale trials in southeast Queensland, Australia. The pyrethroid bifenthrin was evaluated as a potential new protectant in combination with the organophosphate chlorpyrifos-methyl, which is already registered for control of several insect pests of stored cereals. Sorghum (approximately 200 metric tons) was treated after both the 1999 and 2000 harvests and sampled at intervals to assess treatment efficacy and residue decline during up to 7 mo of storage. Generally, test strains of the beetles Rhyzopertha dominica (F.), Tribolium castaneum (Herbst), Oryzaephilus surinamensis (L), and Cryptolestes ferrugineus (Stephens) were prevented from producing live progeny for up to 7 mo. The treatment failed against one strain of R. dominica known to be resistant to bioresmethrin and organophosphates. Two malathion-resistant strains of O. surinamensis were marginally controlled with 94-100% fewer adult progeny produced. For psocids, no strains of Liposcelis bostrychophila Badonnel, Liposcelis decolor (Pearman), or Liposcelis paeta Pearman produced live progeny, although the control of a field strain of Liposcelis entomophila (Enderlein) was generally poor. Results show that this treatment should protect sorghum for at least 7 mo against most prevalent strains of grain insect in eastern Australia, although control may be limited in areas in which L. entomophila or pyrethroid-resistant R. dominica are present. 相似文献
40.
Drosophila perlecan modulates FGF and hedgehog signals to activate neural stem cell division 总被引:3,自引:0,他引:3
Park Y Rangel C Reynolds MM Caldwell MC Johns M Nayak M Welsh CJ McDermott S Datta S 《Developmental biology》2003,253(2):247-257
Mutations in the Drosophila trol gene cause cell cycle arrest of neuroblasts in the larval brain. Here, we show that trol encodes the Drosophila homolog of Perlecan and regulates neuroblast division by modulating both FGF and Hh signaling. Addition of human FGF-2 to trol mutant brains in culture rescues the trol proliferation phenotype, while addition of a MAPK inhibitor causes cell cycle arrest of the regulated neuroblasts in wildtype brains. Like FGF, Hh activates stem cell division in the larval brain in a Trol-dependent fashion. Coimmunoprecipitation studies are consistent with interactions between Trol and Hh and between mammalian Perlecan and Shh that are not competed with heparin sulfate. Finally, analyses of mutations in trol, hh, and ttv suggest that Trol affects Hh movement. These results indicate that Trol can mediate signaling through both of the FGF and Hedgehog pathways to control the onset of stem cell proliferation in the developing nervous system. 相似文献