全文获取类型
收费全文 | 1252篇 |
免费 | 84篇 |
国内免费 | 1篇 |
出版年
2023年 | 8篇 |
2022年 | 19篇 |
2021年 | 39篇 |
2020年 | 28篇 |
2019年 | 27篇 |
2018年 | 34篇 |
2017年 | 26篇 |
2016年 | 41篇 |
2015年 | 48篇 |
2014年 | 75篇 |
2013年 | 87篇 |
2012年 | 87篇 |
2011年 | 97篇 |
2010年 | 63篇 |
2009年 | 44篇 |
2008年 | 52篇 |
2007年 | 52篇 |
2006年 | 44篇 |
2005年 | 48篇 |
2004年 | 33篇 |
2003年 | 28篇 |
2002年 | 25篇 |
2001年 | 29篇 |
2000年 | 22篇 |
1999年 | 22篇 |
1998年 | 9篇 |
1996年 | 9篇 |
1994年 | 8篇 |
1992年 | 15篇 |
1991年 | 9篇 |
1990年 | 10篇 |
1989年 | 10篇 |
1988年 | 12篇 |
1987年 | 7篇 |
1986年 | 12篇 |
1985年 | 6篇 |
1984年 | 12篇 |
1983年 | 7篇 |
1982年 | 9篇 |
1981年 | 5篇 |
1980年 | 8篇 |
1979年 | 13篇 |
1978年 | 11篇 |
1977年 | 7篇 |
1976年 | 7篇 |
1975年 | 8篇 |
1974年 | 5篇 |
1973年 | 10篇 |
1972年 | 6篇 |
1969年 | 5篇 |
排序方式: 共有1337条查询结果,搜索用时 250 毫秒
101.
Dutta T Sengupta R Sahoo R Sinha Ray S Bhattacharjee A Ghosh S 《Letters in applied microbiology》2007,44(2):206-211
AIMS: The enzymatic hydrolysis of xylan has potential economic and environment-friendly applications. Therefore, attention is focused here on the discovery of new extremophilic xylanase in order to meet the requirements of industry. METHODS AND RESULTS: An extracellular xylanase was purified from the culture filtrate of P. citrinum grown on wheat bran bed in solid substrate fermentation. Single step purification was achieved using hydrophobic interaction chromatography. The purified enzyme showed a single band on SDS-PAGE with an apparent molecular weight of c. 25 kDa and pI of 3.6. Stimulation of the activity by beta mercaptoethanol, dithiotheritol (DTT) and cysteine was observed. Moderately thermostable xylanase showed optimum activity at 50 degrees C at pH 8.5. CONCLUSION: Xylanase purified from P. citrinum was alkaliphilic and moderately thermostable in nature. SIGNIFICANCE AND IMPACT OF THE STUDY: The present work reports for the first time the purification and characterization of a novel endoglucanase free alkaliphilic xylanase from the alkali tolerant fungus Penicillium citrinum. The alkaliphilicity and moderate thermostability of this xylanase may have potential implications in paper and pulp industries. 相似文献
102.
Aloe vera has wide spread use in health products, and despite several reports on the whole plant and inner gel, little work has been
performed on the leaf exudate. Our aim was to evaluate the in vitro efficacy of Aloe vera leaf exudate (AVL) in leishmaniasis. Irrespective of the disease manifestation, promastigotes from strains responsible for
cutaneous, mucocutaneous, and visceral leishmaniasis were susceptible to AVL and their IC50 ranged from 100 to 180 μg/ml. In axenic amastigotes cultured from a L. donovani strain 2001 responsible for visceral leishmaniasis, the IC50 was 6.0 μg/ml. AVL caused activation of host macrophages evident by an increased release of members of reactive oxygen species
that was attenuated by preincubation with free radical scavengers. Collectively, our data indicates that AVL, via its direct
leishmanicidal activity which can be further enhanced by activation of host macrophages, is an effective antileishmanial agent
meriting further pharmacological investigations. 相似文献
103.
Kaushal DC Kaushal NA Narula A Kumar N Puri SK Dutta S Lanar DE 《Indian journal of biochemistry & biophysics》2007,44(6):429-436
Plasmodium vivax is one of the most widely distributed human malaria parasites and due to drug-resistant strains, its incidence and prevalence has increased, thus an effective vaccine against the parasites is urgently needed. One of the major constraints in developing P. vivax vaccine is the lack of suitable in vivo models for testing the protective efficacy of the vaccine. P. vivax and P. cynomolgi bastianelli are the two closely related malaria parasites and share a similar clinical course of infection in their respective hosts. The merozoite surface protein-1 (MSP-1) of these parasites has found to be protective in a wide range of host-parasite systems. P. vivax MSP-1 is synthesized as 200 kDa polypeptide and processed just prior to merozoite release from the erythrocytes into smaller fragments. The C- terminal 42 kDa cleavage product of MSP-1 (MSP-1(42)) is present on the surface of merozoites and a major candidate for blood stage malaria vaccine. In the present study, we have biochemically and immunologically characterized the soluble and refolded 42 kDa fragment of MSP-1 of P. vivax (PvMSP-1(42)) and P. cynomolgi B (PcMSP-1(42)). SDS-PAGE analysis showed that both soluble and refolded E. coli expressed P. vivax and P. cynomolgi B MSP-1(42) proteins were homogenous in nature. The soluble and refolded MSP-1(42) antigens of both parasites showed high reactivity with protective monkey sera and conformation-specific monoclonal antibodies against P. cynomolgi B and P. vivax MSP-1(42) antigens. Immunization of BALB/c mice with these antigens resulted in the production of high titres of cross-reactive antibodies primarily against the conformational epitopes of MSP-1(42) protein. The immune sera from rhesus monkeys. immunized with soluble and refolded MSP-1(42) antigens of both parasites also showed high titered cross-reactive antibodies against MSP-1(42) conformational epitopes. These results suggested that the soluble and refolded forms of E. coli expressed P. vivax MSP-1(42) antigens were highly immunogenic and thus a viable candidate for vaccine studies. 相似文献
104.
Ray SS Tejero J Wang ZQ Dutta T Bhattacharjee A Regulski M Tully T Ghosh S Stuehr DJ 《Biochemistry》2007,46(42):11857-11864
Although nitric oxide (NO) is important for cell signaling and nonspecific immunity in the fruit fly Drosophila melanogaster, little is known about its single NO synthase (dNOS). We expressed the oxygenase domain of dNOS (dNOSoxy), characterized its spectroscopic, kinetic, and catalytic properties, and interpreted them in light of a global kinetic model for NO synthesis. Single turnover reactions with ferrous dNOSoxy showed it could convert Arg to N'omega-hydroxy-l-arginine (NOHA), or NOHA to citrulline and NO, when it was given 6R-tetrahydrobiopterin and O2. The dNOSoxy catalyzed Arg hydroxylation and NOHA oxidation at rates that matched or exceeded the rates catalyzed by the three mammalian NOSoxy enzymes. Consecutive heme-dioxy, ferric heme-NO, and ferric heme species were observed in the NOHA reaction of dNOSoxy, indicating that its catalytic mechanism is the same as in the mammalian NOS. However, NO dissociation from dNOSoxy was 4 to 9 times faster than that from the mammalian NOS enzymes. In contrast, the dNOSoxy ferrous heme-NO complex was relatively unreactive toward O2 and in this way was equivalent to the mammalian neuronal NOS. Our data show that dNOSoxy has unique settings for the kinetic parameters that determine its NO synthesis. Computer simulations reveal that these unique settings should enable dNOS to be a more efficient and active NO synthase than the mammalian NOS enzymes, which may allow it to function more broadly in cell signaling and immune functions in the fruit fly. 相似文献
105.
106.
Effect of feeding Jerusalem artichoke (Helianthus tuberosus) root as prebiotic on nutrient utilization,fecal characteristics and serum metabolite profile of captive Indian leopard (Panthera pardus fusca) fed a meat‐on‐bone diet
下载免费PDF全文
![点击此处可从《Zoo biology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
S.K. Pradhan A. Das S.S. Kullu M. Saini A.K. Pattanaik N. Dutta A.K. Sharma 《Zoo biology》2015,34(2):153-162
107.
Samit Kumar Dutta Pedro Serrano Andrew Proudfoot Michael Geralt Bill Pedrini Kurt Wüthrich 《Journal of biomolecular NMR》2015,61(1):47-53
A standard set of three APSY-NMR experiments has been used in daily practice to obtain polypeptide backbone NMR assignments in globular proteins with sizes up to about 150 residues, which had been identified as targets for structure determination by the Joint Center for Structural Genomics (JCSG) under the auspices of the Protein Structure Initiative (PSI). In a representative sample of 30 proteins, initial fully automated data analysis with the software UNIO-MATCH-2014 yielded complete or partial assignments for over 90 % of the residues. For most proteins the APSY data acquisition was completed in less than 30 h. The results of the automated procedure provided a basis for efficient interactive validation and extension to near-completion of the assignments by reference to the same 3D heteronuclear-resolved [1H,1H]-NOESY spectra that were subsequently used for the collection of conformational constraints. High-quality structures were obtained for all 30 proteins, using the J-UNIO protocol, which includes extensive automation of NMR structure determination. 相似文献
108.
Samit Kumar Dutta Pedro Serrano Michael Geralt Herbert L. Axelrod Qingping Xu Scott A. Lesley Adam Godzik Ashley M. Deacon Marc‐André Elsliger Ian A. Wilson Kurt Wüthrich 《Protein science : a publication of the Protein Society》2015,24(10):1600-1608
Flavodoxins in combination with the flavin mononucleotide (FMN) cofactor play important roles for electron transport in prokaryotes. Here, novel insights into the FMN‐binding mechanism to flavodoxins‐4 were obtained from the NMR structures of the apo‐protein from Lactobacillus acidophilus (YP_193882.1) and comparison of its complex with FMN. Extensive reversible conformational changes were observed upon FMN binding and release. The NMR structure of the FMN complex is in agreement with the crystal structure (PDB ID: 3EDO ) and exhibits the characteristic flavodoxin fold, with a central five‐stranded parallel β–sheet and five α‐helices forming an α/β‐sandwich architecture. The structure differs from other flavoproteins in that helix α2 is oriented perpendicular to the β‐sheet and covers the FMN‐binding site. This helix reversibly unfolds upon removal of the FMN ligand, which represents a unique structural rearrangement among flavodoxins. 相似文献
109.
Anwesha Sanyal Andy J. Chen Ernesto S. Nakayasu Cheri S. Lazar Erica A. Zbornik Carolyn A. Worby Antonius Koller Seema Mattoo 《The Journal of biological chemistry》2015,290(13):8482-8499
The maintenance of endoplasmic reticulum (ER) homeostasis is a critical aspect of determining cell fate and requires a properly functioning unfolded protein response (UPR). We have discovered a previously unknown role of a post-translational modification termed adenylylation/AMPylation in regulating signal transduction events during UPR induction. A family of enzymes, defined by the presence of a Fic (filamentation induced by cAMP) domain, catalyzes this adenylylation reaction. The human genome encodes a single Fic protein, called HYPE (Huntingtin yeast interacting protein E), with adenylyltransferase activity but unknown physiological target(s). Here, we demonstrate that HYPE localizes to the lumen of the endoplasmic reticulum via its hydrophobic N terminus and adenylylates the ER molecular chaperone, BiP, at Ser-365 and Thr-366. BiP functions as a sentinel for protein misfolding and maintains ER homeostasis. We found that adenylylation enhances BiP''s ATPase activity, which is required for refolding misfolded proteins while coping with ER stress. Accordingly, HYPE expression levels increase upon stress. Furthermore, siRNA-mediated knockdown of HYPE prevents the induction of an unfolded protein response. Thus, we identify HYPE as a new UPR regulator and provide the first functional data for Fic-mediated adenylylation in mammalian signaling. 相似文献
110.
Clathrin‐mediated endocytosis (CME) and clathrin‐independent endocytosis (CIE) co‐exist in most cells but little is known about their communication and coordination. Here we show that when CME was inhibited, endocytosis by CIE continued but endosomal trafficking of CIE cargo proteins was altered. CIE cargo proteins that normally traffic directly into Arf6‐associated tubules after internalization and avoid degradation (CD44, CD98 and CD147) now trafficked to lysosomes and were degraded. The endosomal tubules were also absent and Arf6‐GTP levels were elevated. The altered trafficking, loss of the tubular endosomal network and elevated Arf6‐GTP levels caused by inhibition of CME were rescued by expression of Rab35, a Rab associated with clathrin‐coated vesicles, or its effector ACAPs, Arf6 GTPase activating proteins (GAP) that inactivate Arf6. Furthermore, siRNA knockdown of Rab35 recreated the phenotype of CME ablation on CIE cargo trafficking without altering endocytosis of transferrin. These observations suggest that Rab35 serves as a CME detector and that loss of CME, or Rab35 input, leads to elevated Arf6‐GTP and shifts the sorting of CIE cargo proteins to lysosomes and degradation. 相似文献