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51.
Small hydroxyethylene-based peptidomimetics inhibiting both HIV-1 and C. albicans aspartic proteases
Tossi A Benedetti F Norbedo S Skrbec D Berti F Romeo D 《Bioorganic & medicinal chemistry》2003,11(22):4719-4727
We have extended a highly flexible method for rapidly assembling aspartic protease inhibitors to produce symmetric and asymmetric monohydroxyethylene peptidomimetics. This method is based on the prior synthesis of the central non-cleavable peptide-bond isostere [NH(2)-P(1)psiP1'-NH(2); psi=hydroxyethylene isostere, HNCH(Bz)CHOHCH(2)CH(Bz)NH], with the possibility of accurately controlling its stereochemistry (S,S,S or S,R,S), and subsequently adding appropriate flanking units, chosen from commercially available amino acids, aromatic carboxylic acids, or phenoxyacetic acid (Poa) derivatives. The method was used to make asymmetric inhibitors of general formula Kyn-Xaa-PhepsiPhe-dmPoa, (Kyn=kynurenic acid, Xaa=Val, Thr or D-thienylglycine, M(r)=716-754) and symmetric inhibitors of formula xPoa-PhepsiPhe-xPoa (xPoa=Poa or dimethyl-, hydroxy-, formyl- or acetyl-Poa, M(r)=553-609), with logP(o/w) values ranging from 4.1 to 7.6. Inhibition of HIV-PR did not depend on the stereochemistry of the hydroxyl group, while it depended markedly on the substituents present on the Poa residues, with dmPoa being preferred over Poa or its more hydrophilic derivatives. Conversely, inhibition of Candida albicans Sap2 was higher for the S,S,S epimers, and Poa or its hydrophilic derivatives were preferred over dmPoa. 相似文献
52.
Katarína Šoltys Matej Planý Paola Biocca Valentina Vianello Mária Bučková Andrea Puškárová Maria Carla Sclocchi Piero Colaizzi Marina Bicchieri Domenico Pangallo Flavia Pinzari 《Environmental microbiology》2020,22(4):1517-1534
A multidisciplinary approach was carried out in order to study the biodeterioration and the associated microbiome of a XVIII Century wax seal coloured with minium. A small wax seal fragment was observed by scanning electron microscopy combined with energy dispersive spectroscopy in non-destructive mode. The same object was analysed by Raman and Fourier-transform infrared spectroscopy. The identification of the microbiota growing on the seal was performed with both a culture-dependent strategy, combined with hydrolytic assays, and high-throughput sequencing using the MinION platform. The whole bacterial 16S rRNA gene and the fungal markers ITS and 28S rRNA were targeted. It was observed that the carnauba wax coloured with lead tetroxide (minium) was covered by a biofilm consisting of a network of filaments and other structures of microbial origin. The culture-dependent and culture-independent investigations showed the presence of a complex microbiota composed mainly by fungal members, which demonstrated interesting properties related to lipids and lead processing. The formation of lead soaps and secondary biogenic minerals was also described. 相似文献
53.
D J Hanahan R D Taverna D D Flynn J E Ekholm 《Biochemical and biophysical research communications》1978,84(4):1009-1015
This paper presents the first unambiguous demonstration that a unique protein isolated from the hemolysate of human erythrocytes is responsible for increasing both the apparent Ca2+ ion affinity and maximum rate of ATP hydrolysis of the membrane-bound ATPase. Unlike previous reports where an unpurified extract from red blood cells was used to activate the ATPase, our results clearly demonstrate that a single protein species, whether initially associated with or added back to the membrane is responsible for the observed changes in ATPase activity. 相似文献
54.
John F. Brandts Richard D. Taverna Easwara Sadasivan Kathryn A. Lysko 《生物化学与生物物理学报:生物膜》1978,512(3):566-578
Differential scanning calorimetry has been used to study several structural transitions of the human erythrocyte membrane. Earlier studies have shown that one of these transitions (the A transition) is due to the thermal unfolding of spectrin on the membrane. In this paper, it is shown that two of the other transitions (B and C) exhibit a high sensitivity to a local anesthetic, benzyl alcohol. Increasing the ionic strength of the suspending medium results in a splitting of the B transition into two independent transitions (B1 and B2). It is found that one of these (B2) is associated with titrating groups, since the midpoint for the transitions shifts by about 20°C, with an apparent near 7.5. Extensive bilateral proteolysis by papain causes a drastic decrease in the size of all transitions except the C transition, which remains unaltered. On the other hand, treatment with phospholipase A2 largely affects the C transition, causing its disappearance. Because of the lack of sensitivity to proteolysis and the high sensitivity to phospholipase, it appears that the C transition has a large extent of ‘lipid involvement’. It might result from the melting of a small fraction of phospholipid which exists in a crystalline state under physiological conditions. Alternatively, the C transition could arise from changes in protein-lipid interactions or from lipid-dependent changes in protein-protein interactions, providing one assumes that only protease-resistant portions of membrane proteins are participating. 相似文献
55.
Vitamin E reduces amyloidosis and improves cognitive function in Tg2576 mice following repetitive concussive brain injury 总被引:3,自引:0,他引:3
Conte V Uryu K Fujimoto S Yao Y Rokach J Longhi L Trojanowski JQ Lee VM McIntosh TK Praticò D 《Journal of neurochemistry》2004,90(3):758-764
Traumatic brain injury is a well-recognized environmental risk factor for developing Alzheimer's disease. Repetitive concussive brain injury (RCBI) exacerbates brain lipid peroxidation, accelerates amyloid (Abeta) formation and deposition, as well as cognitive impairments in Tg2576 mice. This study evaluated the effects of vitamin E on these four parameters in Tg2576 mice following RCBI. Eleven-month-old mice were randomized to receive either regular chow or chow-supplemented with vitamin E for 4 weeks, and subjected to RCBI (two injuries, 24 h apart) using a modified controlled cortical impact model of closed head injury. The same dietary regimens were maintained up to 8 weeks post-injury, when the animals were killed for biochemical and immunohistochemical analyses after behavioral evaluation. Vitamin E-treated animals showed a significant increase in brain vitamin E levels and a significant decrease in brain lipid peroxidation levels. After RBCI, compared with the group on regular chow, animals receiving vitamin E did not show the increase in Abeta peptides, and had a significant attenuation of learning deficits. This study suggests that the exacerbation of brain oxidative stress following RCBI plays a mechanistic role in accelerating Alphabeta accumulation and behavioral impairments in the Tg2576 mice. 相似文献
56.
Martina Bernardi Elena Albiero Alberta Alghisi Katia Chieregato Chiara Lievore Domenico Madeo Francesco Rodeghiero Giuseppe Astori 《Cytotherapy》2013,15(8):920-929
Background aimsA medium supplemented with fetal bovine serum (FBS) is of common use for the expansion of human mesenchymal stromal cells (MSCs). However, its use is discouraged by regulatory authorities because of the risk of zoonoses and immune reactions. Human platelet lysate (PL) obtained by freezing/thawing disruption of platelets has been proposed as a possible substitute of FBS. The process is time-consuming and not well standardized. A new method for obtaining PL that is based on the use of ultrasound is proposed.MethodsPlatelet sonication was performed by submerging platelet-containing plastic bags in an ultrasonic bath. To evaluate platelet lysis we measured platelet-derived growth factor-AB release. PL efficiency was tested by expanding bone marrow (BM)-MSCs, measuring population doubling time, differentiation capacity and immunogenic properties. Safety was evaluated by karyotyping expanded cells.ResultsAfter 30 minutes of sonication, 74% of platelet derived growth factor-AB was released. PL enhanced BM-MSC proliferation rate compared with FBS. The mean cumulative population doubling (cPD) of cells growth in PL at 10%, 7.5% and 5% was better compared with cPD obtained with 10% FBS. PD time (hours) of MSCs with PL obtained by sonication was shorter than for cPD with PL obtained by freezing/thawing (18.9 versus 17.4, P < 0.01). BM mononucleated cells expressed MSC markers and were able to differentiate into adipogenic, osteogenic and chondrogenic lineages. When BM-MSCs and T cells were co-cultured in close contact, immunosuppressive activity of BM-MSCs was maintained. Cell karyotype showed no genetic alterations.ConclusionsThe proposed method for the production of PL by sonication could be a safe, efficient and fast substitute of FBS, without the potential risks of FBS. 相似文献
57.
58.
Rym Zitari-Chatti Noureddine Chatti Domenico Fulgione Immacolata Caiazza Gennaro Aprea Ali Elouaer Khaled Said Teresa Capriglione 《Genetica》2009,136(3):439-447
In this study we analysed mitochondrial DNA variation in Penaeus kerathurus prawns collected from seven locations along a transect across the Siculo–Tunisian region in order to verify if any population
structuring exists over a limited geographical scale and to delineate the putative transition zone with sufficient accuracy.
Partial DNA sequences of COI and 16S genes were analysed. In contrast to the highly conservative 16S gene, the COI sequences
exhibited sufficient diversity for population analysis. The COI gene revealed low levels of haplotype and nucleotide diversities.
The size of the annual landings of this commercial species suggests large population sizes. Hence, the low genetic diversity
detected in this study could indicate a possible reduction in effective population sizes in the past. We detected significant
genetic differentiation between eastern and western populations likely due to restricted gene flow across the Siculo–Tunisian
boundary. We discuss the different evolutionary forces that may have shaped the genetic variation and suggest that the genetic
divide is probably maintained by present-day dispersal limitation.
R. Zitari-Chatti and N. Chatti are contributed equally to the work. 相似文献
59.
Neasham D Gallo V Guarrera S Dunning A Overvad K Tjonneland A Clavel-Chapelon F Linseisen JP Malaveille C Ferrari P Boeing H Benetou V Trichopoulou A Palli D Crosignani P Tumino R Panico S Bueno-De-Mesquita HB Peeters PH van Gib CH Lund E Gonzalez CA Martinez C Dorronsoro M Barricarte A Navarro C Quiros JR Berglund G Jarvholm B Khaw KT Key TJ Bingham S Diaz TM Riboli E Matullo G Vineis P 《DNA Repair》2009,8(1):60-71
We followed-up for mortality and cancer incidence 1088 healthy non-smokers from a population-based study, who were characterized for 22 variants in 16 genes involved in DNA repair pathways. Follow-up was 100% complete. The association between polymorphism and mortality or cancer incidence was analyzed using Cox Proportional Hazard regression models. Ninety-five subjects had died in a median follow-up time of 78 months (inter-quartile range 59-93 months). None of the genotypes was clearly associated with total mortality, except variants for two Double-Strand Break DNA repair genes, XRCC3 18067 C>T (rs#861539) and XRCC2 31479 G>A (rs#3218536). Adjusted hazard ratios were 2.25 (1.32-3.83) for the XRCC3 C/T genotype and 2.04 (1.00-4.13) for the T/T genotype (reference C/C), and 2.12 (1.14-3.97) for the XRCC2 G/A genotype (reference G/G). For total cancer mortality, the adjusted hazard ratios were 3.29 (1.23-7.82) for XRCC3 C/T, 2.84 (0.81-9.90) for XRCC3 T/T and 3.17 (1.21-8.30) for XRCC2 G/A. With combinations of three or more adverse alleles, the adjusted hazard ratio for all cause mortality was 17.29 (95% C.I. 8.13-36.74), and for all incident cancers the HR was 5.28 (95% C.I. 2.17-12.85). Observations from this prospective study suggest that polymorphisms of genes involved in the repair of DNA double-strand breaks significantly influence the risk of cancer and non-cancer disease, and can influence mortality. 相似文献
60.
De Luca A Gallo M Aldinucci D Ribatti D Lamura L D'Alessio A De Filippi R Pinto A Normanno N 《Journal of cellular physiology》2011,226(8):2131-2138
Increasing evidence suggests that bone marrow-derived mesenchymal stem cells (MSCs) are recruited into the stroma of developing tumors where they contribute to cancer progression. MSCs produce different growth factors that sustain tumor-associated neo-angiogenesis. Since the majority of carcinomas secrete ligands of the epidermal growth factor receptor (EGFR), we assessed the role of EGFR signaling in regulating the release of angiogenic factors in MSCs. Treatment of human primary MSCs and of the human osteoblastic cell line hFOB with transforming growth factor α (TGF-α), one of the main ligands of the EGFR, significantly induced activation of this receptor and of different intracellular signaling proteins, including the PI3K/AKT and the MEK/MAPK pathways. TGF-α induced a significant increase in the levels of secretion of vascular endothelial growth factor in both MSCs and hFOB. Conditioned medium from TGF-α treated MSCs showed an higher in vivo angiogenic effect as compared with medium from untreated cells. Treatment of MSCs with TGF-α also produced a significant increase in the secretion of other angiogenic growth factors such as angiopoietin-2, granulocyte-colony stimulating factor, hepatocyte growth factor, interleukin (IL)-6, IL-8, and platelet-derived growth factor-BB. Using selective MEK and PI3K inhibitors, we found that both MEK/MAPK and the PI3K/AKT signaling pathways mediate the ability of TGF-α to induce secretion of angiogenic factors in MSCs. Finally, stimulation with TGF-α increased the ability of MSCs to induce migration of MCF-7 breast cancer cells. These data suggest that EGFR signaling regulates the ability of MSCs to sustain cancer progression through the release of growth factors that promote neo-angiogenesis and tumor cell migration. 相似文献