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201.
Zhang?Lijuan Jifu?Liu Hao?Zhang Shanshan?Wu Lingyun?Huang Dacheng?He Xueyuan?XiaoEmail author 《中国科学C辑(英文版)》2005,48(6):641-647
There are multiple reports of autoimmune response in patients with lung cancer. To investigate whether a novel autoantibody
is present in patients with lung cancer and evaluate its clinical diagnostic and prognostic value, sera from 10 patients with
lung cancer and 10 normal individuals were analyzed using immunofluorescence and Western blotting. It was found that one serum
sample from the patients with squamous carcinoma gave a fine speckled pattern staining in nucleus and had a high titer antinuclear
autoantibody which could recognize 31 kD of nuclear protein isolated from both cancer cells and normal cells. The same patient’s
serum was further used to immunoprecipitate the target antigen. The protein bands were excised from the SDS-PAGE gels and
were analyzed with a Qstar Pulser I Quadrupole time-flight mass spectrometer, and the 31 kD target antigen was identified
as U1-AsnRNP. To test the prevalence of anti-U1-AsnRNP antibody, sera from 93 patients including 36 squmaous carcinomas (SCC),
26 adenocarcinomas (Ad), and 31 small cell carcinomas (SCLC) were screened by Western blotting. The results demonstrated that
anti-U1-A snRNP antibody was present in 50% of SCC sera, 26.9% of Ad sera and 54.8% of SCLC sera. In this paper, we report
for the first time that anti-U1-AsnRNP antibody could be detected in the patients with lung cancer. 相似文献
202.
Natasha Wood Tanmoy Bhattacharya Brandon F. Keele Elena Giorgi Michael Liu Brian Gaschen Marcus Daniels Guido Ferrari Barton F. Haynes Andrew McMichael George M. Shaw Beatrice H. Hahn Bette Korber Cathal Seoighe 《PLoS pathogens》2009,5(5)
The pattern of viral diversification in newly infected individuals provides information about the host environment and immune responses typically experienced by the newly transmitted virus. For example, sites that tend to evolve rapidly across multiple early-infection patients could be involved in enabling escape from common early immune responses, could represent adaptation for rapid growth in a newly infected host, or could represent reversion from less fit forms of the virus that were selected for immune escape in previous hosts. Here we investigated the diversification of HIV-1 env coding sequences in 81 very early B subtype infections previously shown to have resulted from transmission or expansion of single viruses (n = 78) or two closely related viruses (n = 3). In these cases, the sequence of the infecting virus can be estimated accurately, enabling inference of both the direction of substitutions as well as distinction between insertion and deletion events. By integrating information across multiple acutely infected hosts, we find evidence of adaptive evolution of HIV-1 env and identify a subset of codon sites that diversified more rapidly than can be explained by a model of neutral evolution. Of 24 such rapidly diversifying sites, 14 were either i) clustered and embedded in CTL epitopes that were verified experimentally or predicted based on the individual''s HLA or ii) in a nucleotide context indicative of APOBEC-mediated G-to-A substitutions, despite having excluded heavily hypermutated sequences prior to the analysis. In several cases, a rapidly evolving site was embedded both in an APOBEC motif and in a CTL epitope, suggesting that APOBEC may facilitate early immune escape. Ten rapidly diversifying sites could not be explained by CTL escape or APOBEC hypermutation, including the most frequently mutated site, in the fusion peptide of gp41. We also examined the distribution, extent, and sequence context of insertions and deletions, and we provide evidence that the length variation seen in hypervariable loop regions of the envelope glycoprotein is a consequence of selection and not of mutational hotspots. Our results provide a detailed view of the process of diversification of HIV-1 following transmission, highlighting the role of CTL escape and hypermutation in shaping viral evolution during the establishment of new infections. 相似文献
203.
204.
Hydroxylated analogues of the orally active broad spectrum antifungal, Sch 51048 (1), and the discovery of posaconazole [Sch 56592; 2 or (S,S)-5 总被引:1,自引:0,他引:1
Bennett F Saksena AK Lovey RG Liu YT Patel NM Pinto P Pike R Jao E Girijavallabhan VM Ganguly AK Loebenberg D Wang H Cacciapuoti A Moss E Menzel F Hare RS Nomeir A 《Bioorganic & medicinal chemistry letters》2006,16(1):186-190
As part of a detailed study, the syntheses, biological activities, and pharmacokinetic properties of hydroxylated analogues of the previously described broad spectrum antifungal agents, Sch 51048 (1), Sch 50001 (3), and Sch 50002 (4), are described. Based on an overall superior profile, one of the alcohols, Sch 56592 (2), was selected for clinical studies. 相似文献
205.
Guo-Hong Yu Lin-Lin Jiang Xue-Feng Ma Zhao-Shi Xu Meng-Meng Liu Shu-Guang Shan Xian-Guo Cheng 《PloS one》2014,9(10)
Zinc finger proteins were involved in response to different environmental stresses in plant species. A typical Cys2/His2-type (C2H2-type) zinc finger gene GmZF1 from soybean was isolated and was composed of 172 amino acids containing two conserved C2H2-type zinc finger domains. Phylogenetic analysis showed that GmZF1 was clustered on the same branch with six C2H2-type ZFPs from dicotyledonous plants excepting for GsZFP1, and distinguished those from monocotyledon species. The GmZF1 protein was localized at the nucleus, and has specific binding activity with EP1S core sequence, and nucleotide mutation in the core sequence of EPSPS promoter changed the binding ability between GmZF1 protein and core DNA element, implying that two amino acid residues, G and C boxed in core sequence TGACAGTGTCA possibly play positive regulation role in recognizing DNA-binding sites in GmZF1 proteins. High accumulation of GmZF1 mRNA induced by exogenous ABA suggested that GmZF1 was involved in an ABA-dependent signal transduction pathway. Over-expression of GmZF1 significantly improved the contents of proline and soluble sugar and decreased the MDA contents in the transgenic lines exposed to cold stress, indicating that transgenic Arabidopsis carrying GmZF1 gene have adaptive mechanisms to cold stress. Over-expression of GmZF1 also increased the expression of cold-regulated cor6.6 gene by probably recognizing protein-DNA binding sites, suggesting that GmZF1 from soybean could enhance the tolerance of Arabidopsis to cold stress by regulating expression of cold-regulation gene in the transgenic Arabidopsis. 相似文献
206.
Kim-Tat Teoh Yu-Lam Siu Wing-Lim Chan Marc A. Schl��ter Chia-Jen Liu J. S. Malik Peiris Roberto Bruzzone Benjamin Margolis B��atrice Nal 《Molecular biology of the cell》2010,21(22):3838-3852
Intercellular tight junctions define epithelial apicobasal polarity and form a physical fence which protects underlying tissues from pathogen invasions. PALS1, a tight junction-associated protein, is a member of the CRUMBS3-PALS1-PATJ polarity complex, which is crucial for the establishment and maintenance of epithelial polarity in mammals. Here we report that the carboxy-terminal domain of the SARS-CoV E small envelope protein (E) binds to human PALS1. Using coimmunoprecipitation and pull-down assays, we show that E interacts with PALS1 in mammalian cells and further demonstrate that the last four carboxy-terminal amino acids of E form a novel PDZ-binding motif that binds to PALS1 PDZ domain. PALS1 redistributes to the ERGIC/Golgi region, where E accumulates, in SARS-CoV–infected Vero E6 cells. Ectopic expression of E in MDCKII epithelial cells significantly alters cyst morphogenesis and, furthermore, delays formation of tight junctions, affects polarity, and modifies the subcellular distribution of PALS1, in a PDZ-binding motif-dependent manner. We speculate that hijacking of PALS1 by SARS-CoV E plays a determinant role in the disruption of the lung epithelium in SARS patients. 相似文献
207.
Zhong J Chuang SC Bianchi R Zhao W Paul G Thakkar P Liu D Fenton AA Wong RK Tiedge H 《PloS one》2010,5(11):e15509
Background
BC RNAs and the fragile X mental retardation protein (FMRP) are translational repressors that have been implicated in the control of local protein synthesis at the synapse. Work with BC1 and Fmr1 animal models has revealed that phenotypical consequences resulting from the absence of either BC1 RNA or FMRP are remarkably similar. To establish functional interactions between BC1 RNA and FMRP is important for our understanding of how local protein synthesis regulates neuronal excitability.Methodology/Principal Findings
We generated BC1−/− Fmr1−/− double knockout (dKO) mice. We examined such animals, lacking both BC1 RNA and FMRP, in comparison with single knockout (sKO) animals lacking either one repressor. Analysis of neural phenotypical output revealed that at least three attributes of brain functionality are subject to control by both BC1 RNA and FMRP: neuronal network excitability, epileptogenesis, and place learning. The severity of CA3 pyramidal cell hyperexcitability was significantly higher in BC1−/− Fmr1−/− dKO preparations than in the respective sKO preparations, as was seizure susceptibility of BC1−/− Fmr1−/− dKO animals in response to auditory stimulation. In place learning, BC1−/− Fmr1−/− dKO animals were severely impaired, in contrast to BC1−/− or Fmr1−/− sKO animals which exhibited only mild deficits.Conclusions/Significance
Our data indicate that BC1 RNA and FMRP operate in sequential-independent fashion. They suggest that the molecular interplay between two translational repressors directly impacts brain functionality. 相似文献208.
209.
210.
The effects of caffeine on receptor-controlled Ca2+ mobilization and turnover of inositol phosphates in human neuroblastoma SK-N-SH cells were studied. Caffeine inhibited both the rise in cytosolic Ca2+ concentration ([Ca2+]i) evoked by muscarinic receptor agonists and the total production of inositol phosphates in a dose-dependent manner, but to different extents. At 10 mM, caffeine inhibited agonist-evoked generation of inositol phosphates almost completely, whereas the agonist-evoked [Ca2+]i rise remained observable after caffeine treatment, in the absence or presence of extracellular Ca2+. Raising the cytosolic cAMP concentration increased the carbachol-induced [Ca2+]i rise, and this effect was abolished in the presence of caffeine. Our data suggested that caffeine may exert two effects on receptor-controlled Ca2+ mobilization: 1) inhibition of inositol phosphate production, 2) augmentation of the size of the releasable Ca2+ pool by elevating cytosolic cAMP concentration. 相似文献