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941.
942.
Björn Schumacher 《BioEssays : news and reviews in molecular, cellular and developmental biology》2009,31(12):1347-1356
Recent evidence from studies on DNA repair systems that are implicated in accelerated aging syndromes, have revealed a mechanism through which low levels of persistent damage might exert beneficial effects for both cancer prevention and longevity assurance. Beneficial effects of adaptive responses to low doses of insults that in higher concentrations show adverse effects are generally referred to as hormesis. There are numerous examples of hormetic effects ranging from mild stresses of irradiation to heat stress, hypergravity, pro‐oxidants, or food restriction. Although the notion of hormesis is supported by many observations in various organisms, at least two major caveats have thus far prevented the application of hormesis for disease prevention in humans. First, the very nature of hormesis using toxins as a treatment regimen harbors the inherent danger of detrimental consequences. Second, the molecular mechanisms through which insults might exert beneficial effects have thus far remained elusive. Here, I discuss a mechanistic basis for hormesis and its implications for cancer prevention and healthy aging. 相似文献
943.
In this study the poly-acid properties of biosynthetic hyaluronan produced by fermentation of Bacillus subtilis have been investigated. Potentiometric titration as well as 1H NMR titration have been used to determine the dissociation constants of the carboxylic group on hyaluronic acid. The intrinsic pKa and pKa, α=0.5 were determined in the presence of 0.1 M salt to be 2.99 and 3.37, respectively. The pKa, α=0.5 was found to be unaffected by variations in the ionic strength which is in good agreement with the fact that at α = 0.5, 50% of the carboxylic moieties on the hyaluronan are charged. On the other hand the intrinsic pKa was found to be dependent on the ionic strength until the Debye-Hückel screening length approaches the length of repeating disaccharide unit of hyaluronic acid.Our findings are in good agreement with previously determined dissociation constants for other sources of hyaluronan. We have also shown that 1H NMR spectroscopy is the preferred method for polyelectrolyte titration because of the ability to isolate the contribution of several ionisable groups on a polymer on molecular level. 相似文献
944.
945.
Bis‐ and Tetrakis(carboxylato)platinum(IV) Complexes with Mixed Axial Ligands – Synthesis,Characterization, and Cytotoxicity 下载免费PDF全文
Björn R. Hoffmeister Michaela Hejl Mahsa S. Adib‐Razavi Michael A. Jakupec Markus Galanski Bernhard K. Keppler 《化学与生物多样性》2015,12(4):559-574
A series of twelve novel diamminetetrakis(carboxylato)platinum(IV) and 18 novel bis(carboxylato)dichlorido(ethane‐1,2‐diamine)platinum(IV) complexes with mixed axial carboxylato ligands was synthesized and characterized by multinuclear 1H‐, 13C‐, 15N‐, and 195Pt‐NMR spectroscopy. Their cytotoxic potential was evaluated (by MTT assay) against three human cancer cell lines derived from ovarian teratocarcinoma (CH1/PA‐1), lung (A549), and colon carcinoma (SW480). In the cisplatin‐sensitive CH1/PA‐1 cancer cell line, diamminetetrakis(carboxylato)platinum(IV) complexes showed IC50 values in the low micromolar range, whereas, for the most lipophilic compounds of the bis(carboxylato)dichlorido(ethane‐1,2‐diamine)platinum(IV) series, IC50 values in the nanomolar range were found. 相似文献
946.
947.
948.
Quantitative proteomics suggests decrease in the secretogranin‐1 cerebrospinal fluid levels during the disease course of multiple sclerosis 下载免费PDF全文
Ann C. Kroksveen Jacob D. Jaffe Elise Aasebø Harald Barsnes Yngvild Bjørlykke Diego Franciotta Hasmik Keshishian Kjell‐Morten Myhr Jill A. Opsahl Vincent van Pesch Charlotte E. Teunissen Øivind Torkildsen Rune J. Ulvik Heidrun Vethe Steven A. Carr Frode S. Berven 《Proteomics》2015,15(19):3361-3369
Multiple sclerosis (MS) is a chronic inflammatory disease of the CNS with unknown cause. Proteins with different abundance in the cerebrospinal fluid (CSF) from relapsing‐remitting MS (RRMS) patients and neurological controls could give novel insight to the MS pathogenesis and be used to improve diagnosis, predict prognosis and disease course, and guide in therapy decisions. We combined iTRAQ labeling and Orbitrap mass spectrometry to discover proteins with different CSF abundance between six RRMS patients and 18 neurological disease controls. From 777 quantified proteins seven were selected as biomarker candidates, namely chitinase‐3‐like protein 1, secretogranin‐1 (Sg1), cerebellin‐1, neuroserpin, cell surface glycoprotein MUC18, testican‐2 and glutamate receptor 4. An independent sample set of 13 early‐MS patients, 13 RRMS patients and 13 neurological controls was used in a multiple reaction monitoring verification study. We found the intracellular calcium binding protein Sg1 to be increased in early‐MS patients compared to RRMS and neurological controls. Sg1 should be included in further studies to elucidate its role in the early phases of MS pathogenesis and its potential as a biomarker for this disease. 相似文献
949.
Saleta Sierra J. Nikolai Dybowski Alejandro Pironti Dominik Heider Lisa Güney Alex Thielen Stefan Reuter Stefan Esser Gerd F?tkenheuer Thomas Lengauer Daniel Hoffmann Herbert Pfister Bj?rn Jensen Rolf Kaiser 《PloS one》2015,10(5)
ObjectivesWe analysed the impact of different parameters on genotypic tropism testing related to clinical outcome prediction in 108 patients on maraviroc (MVC) treatment.Methods87 RNA and 60 DNA samples were used. The viral tropism was predicted using the geno2pheno[coreceptor] and T-CUP tools with FPR cut-offs ranging from 1%-20%. Additionally, 27 RNA and 28 DNA samples were analysed in triplicate, 43 samples with the ESTA assay and 45 with next-generation sequencing. The influence of the genotypic susceptibility score (GSS) and 16 MVC-resistance mutations on clinical outcome was also studied.ResultsConcordance between single-amplification testing compared to ESTA and to NGS was in the order of 80%. Concordance with NGS was higher at lower FPR cut-offs. Detection of baseline R5 viruses in RNA and DNA samples by all methods significantly correlated with treatment success, even with FPR cut-offs of 3.75%-7.5%. Triple amplification did not improve the prediction value but reduced the number of patients eligible for MVC. No influence of the GSS or MVC-resistance mutations but adherence to treatment, on the clinical outcome was detected.ConclusionsProviral DNA is valid to select candidates for MVC treatment. FPR cut-offs of 5%-7.5% and single amplification from RNA or DNA would assure a safe administration of MVC without excluding many patients who could benefit from this drug. In addition, the new prediction system T-CUP produced reliable results. 相似文献
950.
Torbj?rn Elvs?shagen Linn B. Norbom Per ?. Pedersen Sophia H. Quraishi Atle Bj?rnerud Ulrik F. Malt Inge R. Groote Lars T. Westlye 《PloS one》2015,10(5)
BackgroundElucidating the neurobiological effects of sleep and waking remains an important goal of the neurosciences. Recently, animal studies indicated that sleep is important for cell membrane and myelin maintenance in the brain and that these structures are particularly susceptible to insufficient sleep. Here, we tested the hypothesis that a day of waking and sleep deprivation would be associated with changes in diffusion tensor imaging (DTI) indices of white matter microstructure sensitive to axonal membrane and myelin alterations.MethodsTwenty-one healthy adult males underwent DTI in the morning [7:30AM; time point (TP)1], after 14 hours of waking (TP2), and then after another 9 hours of waking (TP3). Whole brain voxel-wise analysis was performed with tract based spatial statistics.ResultsA day of waking was associated with widespread increases in white matter fractional anisotropy, which were mainly driven by radial diffusivity reductions, and sleep deprivation was associated with widespread fractional anisotropy decreases, which were mainly explained by reductions in axial diffusivity. In addition, larger decreases in axial diffusivity after sleep deprivation were associated with greater sleepiness. All DTI changes remained significant after adjusting for hydration measures.ConclusionsThis is the first DTI study of sleep deprivation in humans. Although previous studies have observed localized changes in DTI indices of cerebral microstructure over the course of a few hours, further studies are needed to confirm widespread DTI changes within hours of waking and to clarify whether such changes in white matter microstructure serve as neurobiological substrates of sleepiness. 相似文献