全文获取类型
收费全文 | 4523篇 |
免费 | 328篇 |
专业分类
4851篇 |
出版年
2023年 | 26篇 |
2022年 | 67篇 |
2021年 | 128篇 |
2020年 | 79篇 |
2019年 | 96篇 |
2018年 | 133篇 |
2017年 | 107篇 |
2016年 | 175篇 |
2015年 | 253篇 |
2014年 | 265篇 |
2013年 | 368篇 |
2012年 | 407篇 |
2011年 | 388篇 |
2010年 | 236篇 |
2009年 | 234篇 |
2008年 | 301篇 |
2007年 | 252篇 |
2006年 | 216篇 |
2005年 | 224篇 |
2004年 | 200篇 |
2003年 | 183篇 |
2002年 | 145篇 |
2001年 | 28篇 |
2000年 | 15篇 |
1999年 | 24篇 |
1998年 | 23篇 |
1997年 | 28篇 |
1996年 | 28篇 |
1995年 | 23篇 |
1994年 | 24篇 |
1993年 | 14篇 |
1992年 | 20篇 |
1991年 | 15篇 |
1990年 | 9篇 |
1989年 | 10篇 |
1988年 | 4篇 |
1987年 | 7篇 |
1986年 | 4篇 |
1985年 | 12篇 |
1984年 | 14篇 |
1983年 | 3篇 |
1982年 | 8篇 |
1981年 | 9篇 |
1980年 | 7篇 |
1979年 | 7篇 |
1978年 | 3篇 |
1977年 | 9篇 |
1976年 | 4篇 |
1975年 | 3篇 |
1974年 | 3篇 |
排序方式: 共有4851条查询结果,搜索用时 0 毫秒
21.
22.
We follow up on a suggestion by Rolls and co-workers, that the effects of competitive learning should be assessed on the shape
and number of spatial fields that dentate gyrus (DG) granule cells may form when receiving input from medial entorhinal cortex
(mEC) grid units. We consider a simple non-dynamical model where DG units are described by a threshold-linear transfer function,
and receive feedforward inputs from 1,000 mEC model grid units of various spacing, orientation and spatial phase. Feedforward
weights are updated according to a Hebbian rule as the virtual rodent follows a long simulated trajectory through a single
environment. Dentate activity is constrained to be very sparse. We find that indeed competitive Hebbian learning tends to
result in a few active DG units with a single place field each, rounded in shape and made larger by iterative weight changes.
These effects are more pronounced when produced with thousands of DG units and inputs per DG unit, which the realistic system
has available, than with fewer units and inputs, in which case several DG units persists with multiple fields. The emergence
of single-field units with learning is in contrast, however, to recent data indicating that most active DG units do have multiple
fields. We show how multiple irregularly arranged fields can be produced by the addition of non-space selective lateral entorhinal
cortex (lEC) units, which are modelled as simply providing an additional effective input specific to each DG unit. The mean
number of such multiple DG fields is enhanced, in particular, when lEC and mEC inputs have overall similar variance across
DG units. Finally, we show that in a restricted environment the mean size of the fields is unaltered, while their mean number
is scaled down with the area of the environment.
相似文献
Alessandro TrevesEmail: |
23.
Unravelling natural killer cell function: triggering and inhibitory human NK receptors 总被引:33,自引:0,他引:33 下载免费PDF全文
Natural killer (NK) cells represent a highly specialized lymphoid population characterized by a potent cytolytic activity against tumor or virally infected cells. Their function is finely regulated by a series of inhibitory or activating receptors. The inhibitory receptors, specific for major histocompatibility complex (MHC) class I molecules, allow NK cells to discriminate between normal cells and cells that have lost the expression of MHC class I (e.g., tumor cells). The major receptors responsible for NK cell triggering are NKp46, NKp30, NKp44 and NKG2D. The NK-mediated lysis of tumor cells involves several such receptors, while killing of dendritic cells involves only NKp30. The target-cell ligands recognized by some receptors have been identified, but those to which major receptors bind are not yet known. Nevertheless, functional data suggest that they are primarily expressed on cells upon activation, proliferation or tumor transformation. Thus, the ability of NK cells to lyse target cells requires both the lack of surface MHC class I molecules and the expression of appropriate ligands that trigger NK receptors. 相似文献
24.
Pandini V Caprini G Thomsen N Aliverti A Seeber F Zanetti G 《The Journal of biological chemistry》2002,277(50):48463-48471
Toxoplasma gondii possesses an apicoplast-localized, plant-type ferredoxin-NADP(+) reductase. We have cloned a [2Fe-2S] ferredoxin from the same parasite to investigate the interplay of the two redox proteins. A detailed characterization of the two purified recombinant proteins, particularly as to their interaction, has been performed. The two-protein complex was able to catalyze electron transfer from NADPH to cytochrome c with high catalytic efficiency. The redox potential of the flavin cofactor (FAD/FADH(-)) of the reductase was shown to be more positive than that of the NADP(+)/NADPH couple, thus favoring electron transfer from NADPH to yield reduced ferredoxin. The complex formation between the reductase and ferredoxins from various sources was studied both in vitro by several approaches (enzymatic activity, cross-linking, protein fluorescence quenching, affinity chromatography) and in vivo by the yeast two-hybrid system. Our data show that the two proteins yield an active complex with high affinity, strongly suggesting that the two proteins of T. gondii form a physiological redox couple that transfers electrons from NADPH to ferredoxin, which in turn is used by some reductive biosynthetic pathway(s) of the apicoplast. These data provide the basis for the exploration of this redox couple as a drug target in apicomplexan parasites. 相似文献
25.
Zampini M Pruzzo C Bondre VP Tarsi R Cosmo M Bacciaglia A Chhabra A Srivastava R Srivastava BS 《FEMS microbiology letters》2005,249(2):267-273
Forty-one Tnpho A mutants of Vibrio cholerae O1 classical strain CD81 were analyzed for their ability to interact with chitin particles, Tigriopus fulvus copepods and the Intestine 407 cell line compared to the parent strain. Thirteen mutants were less adhesive than CD81; in particular, T21, T33 and T87 were less adhesive towards all substrates and insensitive to inhibition by N-acetyl glucosamine (GlcNAc). By SDS-PAGE analysis of sarkosyl-insoluble membrane proteins (siMPs) isolated from mutants and parent, it was found that a 53 kDa siMP is missing in T21, T33 and T87 mutants. It is hypothesized that this protein might have the function to mediate adherence to GlcNAc-containing substrates both in the aquatic environment and in human intestine. 相似文献
26.
Raffaella Ponassi Barbara Biasotti Valeria Tomati Silvia Bruno Alessandro Poggi Davide Malacarne Guido Cimoli Annalisa Salis Sarah Pozzi Maurizio Miglino Gianluca Damonte Pietro Cozzini Francesca Spyrakis Barbara Campanini Luca Bagnasco Nicoletta Castagnino Lorenzo Tortolina Anna Mumot Francesco Frassoni Antonio Daga Michele Cilli Federica Piccardi Ilaria Monfardini Miriam Perugini Gabriele Zoppoli Cristina D’Arrigo Raffaele Pesenti Silvio Parodi 《Cell cycle (Georgetown, Tex.)》2012,11(19):3703
27.
Design and expression of peptides with antimicrobial activity against Salmonella typhimurium 下载免费PDF全文
Amalia Porta Anna Maria Petrone Silvana Morello Ilaria Granata Francesca Rizzo Domenico Memoli Alessandro Weisz Bruno Maresca 《Cellular microbiology》2017,19(2)
We showed previously that insertion of Synechocystis Δ12‐desaturase in salmonella's membrane alters membrane physical state (MPS), followed by the expression of stress genes causing inability to survive within murine macrophages (MΦ). Recently, we showed that expression of one membrane lipid domain (MLD) of Δ12‐desaturase (ORF200) interferes with salmonella MPS, causing loss of virulence in mice and immunoprotection. Here, we postulate that an α‐antimicrobial peptide (α‐AMP) intercalates within membrane lipids, and depending on its amino acid sequence, it does so within specific key sensors of MLD. In this study, we choose as target for a putative synthetic AMP, PhoP/PhoQ, a sensor that responds to low Mg2+ concentration. We synthesised a modified DNA fragment coding for an amino acid sequence (NUF) similar to that fragment and expressed it in salmonella typhimurium. We showed that the pattern of gene expression controlled by PhoP/PhoQ highlights dysregulation of pathways involving phospholipids biosynthesis, stress proteins and genes coding for antigens. RNA‐Seq of strain expressing ORF200 showed that the pattern of those genes is also altered here. Accumulation of NUF conferred temporary immunoprotection. This represents a powerful procedure to address synthetic α‐AMPs to a specific MLD generating live non‐virulent bacterial strains. 相似文献
28.
29.
Pietro Cugini Loredana Di Palma Salvatore Di Simone Piernatale Lucia Paola Battisti Alessandro Coppola Giuseppe Leone 《Chronobiology international》1993,10(1):73-78
This study aimed to explore the 24-h patterns of stroke volume, cardiac output, and peripheral vascular resistance along with other correlated variables, such as left ventricular ejection time, ejection velocity index, thoracic fluid index, heart rate, and blood pressure. The study was performed on 12 clinically healthy subjects by means of a noninvasive beat-to-beat monitoring using the thoracic electric bioimpedance technique associated with the automated sphygmomano-metric recording. Time data series were analyzed by means of chronobiological procedures. The results documented the occurrence of a circadian rhythm for all the variables investigated, giving relevance to the beat-to-beat bioperiodicity of cardiac output and peripheral vascular resistance. Temporal quantification of the investigated variables may be useful for a better insight of the chronophysiology of the cardiovascular apparatus. 相似文献
30.
Cavallo D Ursini CL Perniconi B Francesco AD Giglio M Rubino FM Marinaccio A Iavicoli S 《Mutation research》2005,587(1-2):45-51
The continuous introduction of new antineoplastic drugs and their use as complex mixture emphasize the need to carry out correct health risk assessment. The aim of this study was to evaluate genotoxic effects of antineoplastic drugs in nurses (n=25) and pharmacy technicians (n=5) employed in an oncology hospital. The nurses administered antineoplastic drugs in the day-care hospital (n=12) and in the wards (n=13), and pharmacy technicians prepared the drugs in the central pharmacy. We performed the micronucleus (MN) test with lymphocytes and exfoliated buccal cells and conducted traditional analysis of chromosomal aberrations (CA). Thirty healthy subjects were selected as controls. Monitoring of surface contamination with cyclophosphamide, 5-fluorouracil, ifosfamide, cytarabine, and gemcitabine showed the presence of detectable levels only for cyclophosphamide, 5-fluorouracil and ifosfamide. In addition, we measured the 5-fluorouracil metabolite alpha-F-betaalanine in the urine of all subjects and found significant concentrations only in 3 out of 25 nurses. The micronucleus assay with lymphocytes did not show significant differences between exposed and control groups, while the same test with exfoliated buccal cells found higher values in nurses administering antineoplastic drugs than in pharmacy employees. In the CA analysis, we detected in exposed groups a significant increase (about 2.5-fold) of structural CA, particularly breaks (up to 5.0-fold). Our results confirm the genotoxic effect of antineoplastic drugs in circulating blood lymphocytes. Moreover, in exfoliated buccal cells the data show more consistent genetic damage induced during administration of the antineoplastic drugs than during their preparation. The data also stress the use of this non-invasive sampling, to assess occupational exposure to mixture of chemicals at low doses. 相似文献