全文获取类型
收费全文 | 1125篇 |
免费 | 80篇 |
国内免费 | 1篇 |
出版年
2024年 | 2篇 |
2023年 | 10篇 |
2022年 | 11篇 |
2021年 | 45篇 |
2020年 | 22篇 |
2019年 | 24篇 |
2018年 | 59篇 |
2017年 | 51篇 |
2016年 | 67篇 |
2015年 | 79篇 |
2014年 | 70篇 |
2013年 | 91篇 |
2012年 | 114篇 |
2011年 | 107篇 |
2010年 | 54篇 |
2009年 | 41篇 |
2008年 | 53篇 |
2007年 | 43篇 |
2006年 | 33篇 |
2005年 | 18篇 |
2004年 | 17篇 |
2003年 | 17篇 |
2002年 | 19篇 |
2001年 | 15篇 |
2000年 | 9篇 |
1999年 | 14篇 |
1998年 | 3篇 |
1997年 | 5篇 |
1994年 | 5篇 |
1992年 | 10篇 |
1991年 | 5篇 |
1990年 | 3篇 |
1989年 | 3篇 |
1988年 | 4篇 |
1987年 | 4篇 |
1986年 | 4篇 |
1985年 | 9篇 |
1984年 | 7篇 |
1983年 | 4篇 |
1982年 | 5篇 |
1981年 | 6篇 |
1980年 | 2篇 |
1979年 | 7篇 |
1978年 | 3篇 |
1977年 | 4篇 |
1974年 | 4篇 |
1973年 | 6篇 |
1971年 | 4篇 |
1968年 | 3篇 |
1967年 | 2篇 |
排序方式: 共有1206条查询结果,搜索用时 15 毫秒
1.
Páraic ó Cuív Rajesh Gupta Hareshwar P. Goswami Mark Morrison 《Applied and environmental microbiology》2013,79(19):6173-6175
Clostridium thermocellum encodes a cellulosomal, modular, and thermostable serine protease inhibitor (serpin), PinA. PinA stability but not inhibitory activity is affected by the Fn(III) and Doc(I) domains, and PinA is a broad inhibitor of subtilisin-like proteases and may play a key role in protecting the cellulosome from protease attack. 相似文献
2.
3.
Julia I. Gavrilyuk Ulrich Wuellner Syed Salahuddin Rajib K. Goswami Subhash C. Sinha Carlos F. Barbas 《Bioorganic & medicinal chemistry letters》2009,19(14):3716-3720
Irreversible chemical programming of monoclonal aldolase antibody (mAb) 38C2 has been accomplished with β-lactam equipped mono- and bifunctional targeting modules, including a cyclic-RGD peptide linked to either the peptide (d-Lys6)-LHRH or another cyclic RGD unit and a small-molecule integrin inhibitor SCS-873 conjugated to (d-Lys6)LHRH. We also prepared monofunctional targeting modules containing either cyclic RGD or (d-Lys6)-LHRH peptides. Binding of the chemically programmed antibodies to integrin receptors α(v)β(3) and α(v)β(5) and to the luteinizing hormone releasing hormone receptor were evaluated. The bifunctional and bivalent c-RGD/LHRH and SCS-783/LHRH, the monofunctional and tetravalent c-RGD/c-RGD, and the monofunctional bivalent c-RGD chemically programmed antibodies bound specifically to the isolated integrin receptor proteins as well as to integrins expressed on human melanoma M-21 cells. c-RGD/LHRH, SCS-783/LHRH, and LHRH chemically programmed antibodies bound specifically to the LHRH receptors expressed on human ovarian cancer cells. This approach provides an efficient, versatile, and economically viable route to high-valency therapeutic antibodies that target defined combinations of specific receptors. Additionally, this approach should be applicable to chemically programmed vaccines. 相似文献
4.
There is an urgent need for effective prophylactic measures against Mycobacterium tuberculosis (Mtb) infection, particularly given the highly variable efficacy of Bacille Calmette-Guerin (BCG), the only licensed vaccine against tuberculosis (TB). Most studies indicate that cell-mediated immune responses involving both CD4+ and CD8+ T cells are necessary for effective immunity against Mtb. Genetic vaccination induces humoral and cellular immune responses, including CD4+ and CD8+ T-cell responses, against a variety of bacterial, viral, parasitic and tumor antigens, and this strategy may therefore hold promise for the development of more effective TB vaccines. Novel formulations and delivery strategies to improve the immunogenicity of DNA-based vaccines have recently been evaluated, and have shown varying degrees of success. In the present study, we evaluated DNA-launched Venezuelan equine encephalitis replicons (Vrep) encoding a novel fusion of the mycobacterial antigens α-crystallin (Acr) and antigen 85B (Ag85B), termed Vrep-Acr/Ag85B, for their immunogenicity and protective efficacy in a murine model of pulmonary TB. Vrep-Acr/Ag85B generated antigen-specific CD4+ and CD8+ T cell responses that persisted for at least 10 wk post-immunization. Interestingly, parenterally administered Vrep-Acr/Ag85B also induced T cell responses in the lung tissues, the primary site of infection, and inhibited bacterial growth in both the lungs and spleens following aerosol challenge with Mtb. DNA-launched Vrep may, therefore, represent an effective approach to the development of gene-based vaccines against TB, particularly as components of heterologous prime-boost strategies or as BCG boosters. 相似文献
5.
H. K. Goswami Manoj Chandorkar Kakoli Bhattacharya G. Vaidyanath D. Parmar S. Sengupta S. L. Patidar L. K. Sengupta Rajeev Goswami P. N. Sharma 《Human genetics》1990,84(2):172-176
Summary A chromosomal survey using standard lymphocyte cultures employing different media and G-banding techniques was initiated in 1984. This study became particularly important following the tragic gaseous exposure of the population in Bhopal at midnight on 2 December 1984. We have been able to formulate a chromosomal profile for each person whom we have studied; during 1986–1988, 154 persons were examined twice. Among seemingly normal individuals, as many as 20% might possess some chromosomal abnormality; of these, 50% may develop, at a later date, some kind of pathological complication (such as tumours, recurrent abortion or transmission of defects to their offspring). The people exposed to methyl isocyanate have repeatedly shown Robertsonian translocations, mostly in acrocentric chromosomes 13 and 21. Other types of translocations have been studied among all exposed (53) and normal (101) persons; the involvement of chromosomes 5, 9, 11, 14 and 16 is statistically significant (P= <0.001). One of the major clinical symptoms is dyspnoea; we have estimated that almost all seriously dyspnoeic patients have developed at least two categories of chromosomal aberrations, one of which is Robertsonian translocation, in at least 10% metaphases. Our chromosomal survey will be of significance because we are able to identify people with chromosomal aberrations that might be correlated with future pathological consequences of the accident. The chromosomal load that can be sustained with an apparently normal phenotype can also be measured. 相似文献
6.
Effect of hypophysectomy and replacement therapy on fatty acid metabolism in the rat testis 总被引:1,自引:1,他引:0 下载免费PDF全文
1. The influence of pituitary gonadotrophins and of testosterone on the conversion of linoleic acid into other polyunsaturated fatty acids by rat testicular tissue was studied. 2. In immature hypophysectomized rats, follicle-stimulating hormone caused a threefold increase in the incorporation of radioactivity from [1-(14)C]linoleic acid into testicular lipids; the distribution of (14)C in the polyunsaturated fatty acids, however, was not significantly affected. 3. In mature hypophysectomized rats, the hormonal treatments had less pronounced effects on (14)C incorporation into testicular lipids, but caused a significant increase in the percentage of (14)C incorporated into polyunsaturated fatty acids of the omega-6 series, luteinizing hormone and testosterone having the more pronounced influences. 4. A time-course study of the appearance of radioactivity in the ejaculated spermatozoa of rabbits, after they had been given a tracer dose of [1-(14)C]linoleic acid, indicated that incorporation of radioactivity into spermatozoa occurred during all stages of spermatogenesis. 相似文献
7.
Adherence of multiple serovars of Chlamydia trachomatis to a common receptor on HeLa and McCoy cells is mediated by thermolabile protein(s) 总被引:7,自引:0,他引:7
Several aspects of the adherence of purified elementary bodies (EB) of Chlamydia trachomatis to HeLa and to McCoy cells were examined using different techniques, including an ELISA. Serovar-specific, biotinylated monoclonal antibodies were used to detect cell-bound chlamydiae. In addition, purified chlamydiae were biotinylated and their adherence properties were studied. The assays were done at 4 degrees C to exclude the energy-dependent internalization of the cell-bound EB and host-cell membrane recycling that occur at 37 degrees C. Saturation kinetics were routinely observed at 4 degrees C, and the rate of adherence remained linear for approximately 60 min. Lineweaver-Burk analysis of the kinetics data showed that adherence of any one serovar was competitively inhibited by other serovars of C. trachomatis. This competition for the same receptor on the two alternative hosts, HeLa and McCoy, was also seen when the adherence assays were done at 37 degrees C in the presence of sodium azide, an energy poison that inhibits endocytosis of cell-bound chlamydiae. Chlamydiae exposed to 56 degrees C for 5 min, or treated with low doses of trypsin, failed to exhibit competitive inhibition, having suffered considerable loss of the ability to adhere to host-cells. These data suggest that heat- and trypsin-labile chlamydial moieties participate in the adherence reaction, and that oculo-genital serovars of C. trachomatis, including that of lymphogranuloma venereum, attach to the same receptor on the host-cell membrane. 相似文献
8.
Previous studies have established that the 93-kDa protein-tyrosine kinase (PTK) encoded by the human c-fes protooncogene plays an active role in the induction of terminal myeloid differentiation. However, this enzyme is expressed at very low levels in myeloid cells, making isolation of sufficient quantities for detailed biochemical analysis difficult. To overcome this problem, we used the polymerase chain reaction to construct a full-length c-fes cDNA from overlapping 5' and 3' partial cDNA sequences. The c-fes cDNA was expressed at high levels in a baculovirus system, and the catalytically active recombinant c-fes gene product p93c-fes was partially purified by DEAE-Sepharose and tyrosine-agarose chromatography. Recombinant p93c-fes was indistinguishable from the native protein in terms of its apparent molecular weight following SDS-PAGE, catalytic activity, Km for poly(Glu,Tyr)4:1, antigenicity, and phosphopeptide pattern generated with Staphylococcus aureus protease. 相似文献
9.
Juliette Gaëtan Sébastien Halary Maxime Millet Cécile Bernard Charlotte Duval Sahima Hamlaoui Amandine Hecquet Muriel Gugger Benjamin Marie Neha Mehta David Moreira Fériel Skouri-Panet Cynthia Travert Elodie Duprat Julie Leloup Karim Benzerara 《Environmental microbiology》2023,25(3):751-765
The formation of intracellular amorphous calcium carbonates (iACC) has been recently observed in a few cultured strains of Microcystis, a potentially toxic bloom-forming cyanobacterium found worldwide in freshwater ecosystems. If iACC-forming Microcystis are abundant within blooms, they may represent a significant amount of particulate Ca. Here, we investigate the significance of iACC biomineralization by Microcystis. First, the presence of iACC-forming Microcystis cells has been detected in several eutrophic lakes, indicating that this phenomenon occurs under environmental conditions. Second, some genotypic (presence/absence of ccyA, a marker gene of iACC biomineralization) and phenotypic (presence/absence of iACC) diversity have been detected within a collection of strains isolated from one single lake. This illustrates that this trait is frequent but also variable within Microcystis even at a single locality. Finally, one-third of publicly available genomes of Microcystis were shown to contain the ccyA gene, revealing a wide geographic and phylogenetic distribution within the genus. Overall, the present work shows that the formation of iACC by Microcystis is common under environmental conditions. While its biological function remains undetermined, this process should be further considered regarding the biology of Microcystis and implications on the Ca geochemical cycle in freshwater environments. 相似文献
10.
Manab Jyoti Goswami Utpal Dutta Tage Seema Sourav Jyoti Bharali Hage Yanka Hui Tag Pankaj Bharali Dwipen Kakati 《化学与生物多样性》2023,20(2):e202200718
Three underutilized leafy vegetables Sarcochlamys pulcherrima (Roxb.) Gaudich (SP), Ipomoea aquatica Forssk. (IA) and Zanthoxylum rhetsa (Roxb.) DC (ZR) were extracted with different solvents viz. 95 % ethyl alcohol, methanol and hot water. The extracts were evaluated for their antioxidant potential via DPPH, ABTS and FRAP assay along with electroanalytical studies using cyclic voltammetry. The antidiabetic potential was determined by recording their α-amylase and α-glucosidase inhibitory assay. The total phenolic content (TPC), total flavonoid content (TFC) and the liquid chromatography-mass spectrometry (LC/MS) based phytochemical profiles of the extracts were also determined. All three extracts of SP exhibited significant antioxidant capacity. The antidiabetic potential of the IA and ZR extracts was found to be higher than or at par with that of standard acarbose. LC/MS studies reveal the presence of hitherto reported antioxidant and antidiabetic compounds like gamma-aminobutyric acid, cinnamic acid, caffeic acid, α-viniferin, piperlonguminine, niacin, kaempferol, etc., in the extracts. 相似文献