全文获取类型
收费全文 | 2058篇 |
免费 | 154篇 |
国内免费 | 1篇 |
出版年
2023年 | 17篇 |
2022年 | 28篇 |
2021年 | 47篇 |
2020年 | 34篇 |
2019年 | 44篇 |
2018年 | 39篇 |
2017年 | 46篇 |
2016年 | 43篇 |
2015年 | 74篇 |
2014年 | 104篇 |
2013年 | 112篇 |
2012年 | 129篇 |
2011年 | 129篇 |
2010年 | 82篇 |
2009年 | 75篇 |
2008年 | 112篇 |
2007年 | 105篇 |
2006年 | 78篇 |
2005年 | 72篇 |
2004年 | 78篇 |
2003年 | 64篇 |
2002年 | 68篇 |
2001年 | 55篇 |
2000年 | 68篇 |
1999年 | 55篇 |
1998年 | 27篇 |
1997年 | 16篇 |
1996年 | 14篇 |
1995年 | 9篇 |
1994年 | 17篇 |
1993年 | 17篇 |
1992年 | 30篇 |
1991年 | 33篇 |
1990年 | 32篇 |
1989年 | 32篇 |
1988年 | 22篇 |
1987年 | 17篇 |
1986年 | 12篇 |
1985年 | 12篇 |
1984年 | 13篇 |
1983年 | 9篇 |
1982年 | 15篇 |
1979年 | 12篇 |
1978年 | 7篇 |
1977年 | 11篇 |
1976年 | 7篇 |
1975年 | 8篇 |
1974年 | 16篇 |
1973年 | 9篇 |
1971年 | 9篇 |
排序方式: 共有2213条查询结果,搜索用时 15 毫秒
991.
A calcium-activated protease caldonopain in the cytosolic fraction of Leishmania donovani has been found to digest different endogenous proteins when subjected to SDS-PAGE. Gelatin-embedded gel electrophoresis confirms
presence of calcium-dependent protease activity. Ca2+ affects proteolytic activity after 10 h. When host–parasite interaction was conducted in vitro, caldonopain was found to be active after 10 h of incubation with calcium. A 67-kDa protein is specifically digested during
this time and two new proteins of 45 and 36 kDa appeared in SDS-PAGE electrophoregram. This belated action of calcium towards
protease activity may be pre-requisite to facilitate invasion of host tissues and thereby mediate protein metabolism during
survival of this pathogen both independently and intracellularly. It is likely that calcium metabolism in promastigotes and
amastigotes does not propagate in the same manner. Involvement of calcium to initiate caldonopain activity may be critically
associated with signal transduction pathways which may be responsible for the pathobiological action of this parasite. We
propose that caldonopain could be a potential target to develop new chemotherapeutic approach against leishmaniasis. 相似文献
992.
Polycondensations were performed at 70 degrees C in bulk using physically immobilized lipase B from Candida antarctica (CAL-B) as catalyst. Study of copolymerizations between sebacic acid and PEG diols of differing Mn values (200, 400, 600, 1000, 2000, and 10 000) showed that PEG 400 and 600 were most reactive (DP(avg) up to about 6). Increasing the PEG diol chain length from 600 to 1000, 2000, and 10 000 resulted in large decreases in copolymer DP(avg) values. PEG200 diacids (i.e., HOOC-(CH2)x-O-(CH2CH2O)n-(CH2)x-COOH) were successfully synthesized where x was 1, 4, 5, 7, 9, and 11. Study of copolymerizations of these diacids with 1,8-octanediol showed that, by introduction of a five-carbon methylene spacer (x = 5), remarkable increases in the reactivity of PEG200 diacids were achieved. In addition, introduction of this spacer was also effective for increasing the reactivity of PEG diacids of higher molecular weight (i.e., PEG400, 600, and 1000). This work verified the hypothesis that, by conversion of PEG chain ends to structures more closely resembling fatty acids, modified PEG building blocks are obtained that are better recognized as substrates by CAL-B during condensation reactions. 相似文献
993.
Ghosh D Bhattacharya S Mazumder S 《Comparative biochemistry and physiology. Toxicology & pharmacology : CBP》2006,143(4):455-463
The present study was an attempt to elucidate the effect of non-lethal arsenic (As) exposure (1/10 LC50) on different immunologically important organs and cells of a catfish. Clarias batrachus L. were exposed to arsenic trioxide for different time intervals, which resulted in significant, time-dependent changes in total head kidney and splenic leucocyte count (p<0.05) and reduction in the organosomatic indices (p<0.05) of these two important immunocompetent organs. Routine histological studies revealed arsenic induced changes in the cellular composition of head kidney and spleen. Arsenic also induced time-dependent and tissue-specific alterations in T and B cell functioning in catfish. When checked for its effects on macrophages, it was noted that arsenic interfered with bacterial phagocytosis. Furthermore, arsenic affected the general immune status of C. batrachus and rendered the fish immunocompromised and susceptible to pathogens. 相似文献
994.
Hwan Su Yoon Jeremiah D. Hackett Debashish Bhattacharya 《Journal of applied phycology》2006,18(3-5):475-481
Accounting for the diversity of photosynthetic eukaryotes is an important challenge in microbial biology. It has now become clear that endosymbiosis explains the origin of the photosynthetic organelle (plastid) in different algal groups. The first plastid originated from a primary endosymbiosis, whereby a previously non-photosynthetic protist engulfed and enslaved a cyanobacterium. This alga then gave rise to the red, green, and glaucophyte lineages. Algae such as the chlorophyll c-containing chromists gained their plastid through secondary endosymbiosis, in which an existing eukaryotic alga (in this case, a rhodophyte) was engulfed. Another chlorophyll c-containing algal group, the dinoflagellates, is a member of the alveolates that is postulated to be sister to chromists. The plastid in these algae has followed a radically different path of evolution. The peridinin-containing dinoflagellates underwent an unprecedented level of plastid genome reduction with the ca. 16 remaining genes encoded on 1–3 gene minicircles. In this short review, we examine algal plastid diversity using phylogenetic and genomic methods and show endosymbiosis to be a major force in algal evolution. In particular, we focus on the evolution of targeting signals that facilitate the import of nuclear-encoded photosynthetic proteins into the plastid. 相似文献
995.
Zhou P Dragulescu-Andrasi A Bhattacharya B O'Keefe H Vatta P Hyldig-Nielsen JJ Ly DH 《Bioorganic & medicinal chemistry letters》2006,16(18):4931-4935
Guanidine-based peptide nucleic acid (GPNA) monomers and oligomers containing all four natural (adenine (A), cytosine (C), guanine (G), and thymine (T)) and two unnatural (2-thiouracil (sU) and 2,6-diaminopurine (D)) nucleobases have been synthesized. Thermal denaturation study showed that GPNA oligomers containing alternate D-backbone configuration bind sequence-specifically to DNA and, when incubated with mammalian cells, localized specifically to the endoplasmic reticulum (ER). 相似文献
996.
Anil Dangi Satish Vedi Jeetendra Kumar Nag Sameer Paithankar Mahendra Pratap Singh Santosh Kumar Kar Anuradha Dube Shailja Misra‐Bhattacharya 《Proteomics》2009,9(17):4192-4208
Wolbachia is an intracellular endosymbiont of Brugia malayi parasite whose presence is essential for the survival of the parasite. Treatment of B. malayi‐infected jirds with tetracycline eliminates Wolbachia, which affects parasite survival and fitness. In the present study we have tried to identify parasite proteins that are affected when Wolbachia is targeted by tetracycline. For this Wolbachia depleted parasites (B. malayi) were obtained by tetracycline treatment of infected Mongolian jirds (Meriones unguiculatus) and their protein profile after 2‐DE separation was compared with that of untreated parasites harboring Wolbachia. Approximately 100 protein spots could be visualized followed by CBB staining of 2‐D gel and included for comparative analysis. Of these, 54 showed differential expressions, while two new protein spots emerged (of 90.3 and 64.4 kDa). These proteins were subjected to further analysis by MALDI‐TOF for their identification using Brugia coding sequence database composed of both genomic and EST sequences. Our study unravels two crucial findings: (i) the parasite or Wolbachia proteins, which disappeared/down‐regulated appear be essential for parasite survival and may be used as drug targets and (ii) tetracycline treatment interferes with the regulatory machinery vital for parasites cellular integrity and defense and thus could possibly be a molecular mechanism for the killing of filarial parasite. This is the first proteomic study substantiating the wolbachial genome integrity with its nematode host and providing functional genomic data of human lymphatic filarial parasite B. malayi. 相似文献
997.
998.
Two bis-heteroleptic Ru(II) complexes [Ru(bpy)2(pcip)]2+ (1, bpy = 2,2′-bipyridine, pcip = 2-[4-phenylcarboxy]-1H-imidazol[4,5-f][1,10]phenanthroline) and [Ru(phen)2(pcip)]2+ (2, phen = 1,10-phenanthroline), bearing highly conjugated diimine ligands, were prepared and isolated as their PF6 salts. The bpy-derivative 1 showed better photophysical properties (emission quantum yield, lifetime of the emitting state, and the radiative decay rate constant) than the phen-compound 2. These results followed by theoretical calculations at DFT level established a comprehensive understanding between the structural parameters and the photophysical properties, as well as of the influence of π conjugation and the symmetry of the molecules on spectroscopic characteristics. These results provide fundamental photophysical data for selecting ancillary ligands in the design and improvement of Ru-based light-harvesting complexes. 相似文献
999.
Ladiwala AR Perchiacca JM Fishman ZS Bhattacharya M Hickey AM Domigan BG Dordick JS Tessier PM 《Biotechnology and bioengineering》2012,109(7):1869-1874
Protein aggregation is a common problem during the purification and formulation of therapeutic proteins. Here we report that polyphenolic disaccharides are unusually effective at preventing protein aggregation. We find that two polyphenolic glycosides-naringin and rutin-endow diverse proteins with the ability to unfold without aggregating when heated, as well as the ability to refold without aggregating when cooled at low glycoside concentrations (<5 mM). This extreme solubilizing activity is a synergistic combination of the glycone and aglycone moieties, as combinations of polyphenols and sugars fail to suppress aggregation. Moreover, the activity of polyphenolic disaccharides is remarkably specific since their monosaccharide counterparts (as well as other common excipients such as arginine, trehalose, and cyclodextrin) fail to prevent aggregation at similar concentrations (<25 mM). We expect that polyphenolic disaccharides will be valuable additives for enhancing the solubility of proteins in applications plagued by protein aggregation. 相似文献
1000.
Ved Prakash Dwivedi Debapriya Bhattacharya Samit Chatterjee Durbaka Vijay Raghva Prasad Debprasad Chattopadhyay Luc Van Kaer William R. Bishai Gobardhan Das 《The Journal of biological chemistry》2012,287(40):33656-33663
Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), resides and replicates within phagocytes and persists in susceptible hosts by modulating protective innate immune responses. Furthermore, M. tuberculosis promotes T helper 2 (Th2) immune responses by altering the balance of T cell polarizing cytokines in infected cells. However, cytokines that regulate Th2 cell differentiation during TB infection remain unknown. Here we show that IL-1β, produced by phagocytes infected by virulent M. tuberculosis strain H37Rv, directs Th2 cell differentiation. In sharp contrast, the vaccine strain bacille Calmette-Guérin as well as RD-1 and ESAT-6 mutants of H37Rv failed to induce IL-1β and promote Th2 cell differentiation. Furthermore, ESAT-6 induced IL-1β production in dendritic cells (DCs), and CD4+ T cells co-cultured with infected DCs differentiated into Th2 cells. Taken together, our findings indicate that IL-1β induced by RD-1/ESAT-6 plays an important role in the differentiation of Th2 cells, which in turn facilitates progression of TB by inhibiting host protective Th1 responses. 相似文献