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991.
Zhenyu Jia Michael B. Lilly James A. Koziol Xin Chen Xiao-Qin Xia Yipeng Wang Douglas Skarecky Manuel Sutton Anne Sawyers Herbert Ruckle Philip M. Carpenter Jessica Wang-Rodriguez Jun Jiang Mingsen Deng Cong Pan Jian-guo Zhu Christine E. McLaren Michael J. Gurley Chung Lee Michael McClelland Thomas Ahlering Michael W. Kattan Dan Mercola 《PloS one》2014,9(1)
It is difficult to construct a control group for trials of adjuvant therapy (Rx) of prostate cancer after radical prostatectomy (RP) due to ethical issues and patient acceptance. We utilized 8 curve-fitting models to estimate the time to 60%, 65%, … 95% chance of progression free survival (PFS) based on the data derived from Kattan post-RP nomogram. The 8 models were systematically applied to a training set of 153 post-RP cases without adjuvant Rx to develop 8 subsets of cases (reference case sets) whose observed PFS times were most accurately predicted by each model. To prepare a virtual control group for a single-arm adjuvant Rx trial, we first select the optimal model for the trial cases based on the minimum weighted Euclidean distance between the trial case set and the reference case set in terms of clinical features, and then compare the virtual PFS times calculated by the optimum model with the observed PFSs of the trial cases by the logrank test. The method was validated using an independent dataset of 155 post-RP patients without adjuvant Rx. We then applied the method to patients on a Phase II trial of adjuvant chemo-hormonal Rx post RP, which indicated that the adjuvant Rx is highly effective in prolonging PFS after RP in patients at high risk for prostate cancer recurrence. The method can accurately generate control groups for single-arm, post-RP adjuvant Rx trials for prostate cancer, facilitating development of new therapeutic strategies. 相似文献
992.
Shu Xia Xin Fan Zengguang Huang Liang Xia Meng Xiao Rongchang Chen Yingchun Xu Chao Zhuo 《PloS one》2014,9(7)
Objective
To investigate CTX-M genotypes among extended-spectrum β-lactamase-producing Escherichia coli (ESBL-EC) isolated from patients with community-onset and hospital-onset infections in China, their clonality and the distribution of CTX-M variants in different specimens of community-onset and hospital-onset infections.Methods
ESBL-EC isolates were collected from general hospitals from 2011 to 2012 in China. Broth microdilution method antimicrobial susceptibility testing of 16 antibiotics was performed. Clinical data from community-onset and hospital-onset infections due to ESBL-EC were analyzed. ESBL-encoding genes were amplified by PCR and sequenced, and multilocus sequence typing (MLST) was performed for a random selection of predominant CTX-M type strains identified.Results
A total of 1,168 ESBL-EC isolates were obtained from various clinical specimens, 41.7% of which were responsible for causing community-onset infections. The presence of urinary calculi was higher in community-onset infections, whereas malignancy, cardiovascular and cerebrovascular diseases, dementia, chronic renal disease, diabetes mellitus and surgical treatment were found to have higher proportions in hospital-onset infections. There was no significant difference in trauma between community-onset and hospital-onset infections. 96.2% of the isolates were detected to harbor bla CTX-M genes. bla CTX-M-1 group and bla CTX-M-9 group were detected at 40.7% and 48.7% respectively, and both positive group accounted for 10.6%. bla CTX-M-55 (24.8%) and bla CTX-M-15 (18.2%) were the major genotypes in bla CTX-M-1 group while bla CTX-M-14 (46.8%) was predominant in bla CTX-M-9 group. A comparison of bla CTX-M distribution in different specimens between ESBL-EC causing community-onset and hospital-onset infection showed no significant difference. A total of 229 isolates were tested for MLST. ST131 (14%) was the predominant type. ST648, ST405 and ST1193 were also detected.Conclusions
Community-onset ESBL-EC has emerged as a common pathogen in China. CTX-M-14 is the most commonly encountered, CTX-M-55 and CTX-M-15 have spread rapidly. ST131 is the predominant clonal group, and the great diversity of CTX-M-producing isolates of E. coli has emerged in China. 相似文献993.
Yan Zheng Dan-dan Wang Wei Wang Ke Pan Chun-yu Huang Yuan-fang Li Qi-Jing Wang Shu-qiang Yuan Shan-shan Jiang Hai-bo Qiu Yong-ming Chen Xiao-fei Zhang Bai-wei Zhao Cong mai Jian-chuan Xia Zhi-wei Zhou 《PloS one》2014,9(4)
Background
The aim of this study was to investigate the expression and prognostic significance of Uroplakin1A (UPK1A) in gastric adenocarcinoma patients. Functional studies were also analyzed in vitro.Methodology/Principal Findings
Real-time quantitative PCR (RT-qPCR), western blotting, and immunohistochemical (IHC) staining methods were used to analyze the expression of UPK1A in primary gastric adenocarcinoma tissue samples. Compared with matched adjacent non-tumor, the expression of UPK1A in fresh surgical specimens was reduced, which was confirmed by RT-qPCR (P<0.01) and western blotting analysis (P<0.01). The paraffin specimens from a consecutive series of 445 gastric adenocarcinoma patients who underwent surgery between 2003 and 2006 were analyzed by IHC staining. The relationship between UPK1A expression, clinicopathological factors, and survival were evaluated. IHC staining analysis revealed that the reduced expression of UPK1A was observed in 224 cases (50.3%). Additionally, the correlation analysis of clinicopathological factors demonstrated that reduced expression of UPK1A was significantly associated with histological grade (P = 0.022), node metastasis (P<0.001) and tumor node metastasis (TNM) stage (P = 0.008) (7th edition of the International Union Against Cancer (UICC)). Furthermore, Kaplan-Meier survival analysis revealed that the reduced expression of UPK1A was significantly associated with poor prognosis (P = 0.043). Cox hazards model analysis indicated that UPK1A expression was an independent risk factor at the 0.1 level (P = 0.094). The function of UPK1A in cell cycle, migration, and invasion was investigated by overexpressing UPK1A in the MKN45 gastric cancer cell line. The elevated expression of UPK1A cells induced G1 phase arrest and significantly inhibited migration and invasion.Conclusions/Significance
The reduced expression of UPK1A might play a role in the progression of gastric cancer. Thus, UPK1A could be a potential favorable biomarker associated with gastric cancer prognosis. 相似文献994.
995.
996.
Chen X Shang H Qiu X Fujiwara N Cui L Li XM Gao TM Kong J 《Neurochemical research》2012,37(4):835-845
Converging evidence indicates that SOD1 aggregation is a common feature of mutant SOD1-linked fALS, and seems to be directly
related to the gain-of-function toxic property. However, the mechanism inducing the aggregation is not understood. To study
the contribution of oxidative modification of cysteine residues in SOD1 aggregation, we systematically examined the redox
state of SOD1 cysteine residues in the G37R transgenic mouse model at different stages of the disease and under oxidative
stress induced by H2O2. Our data suggest that under normal circumstance, cysteine 111 residue in SOD1 is free; however, under oxidative stress,
it is prone to oxidative modification by providing the thiolate anion (S−). With the progression of the disease, increased
levels of oxidative insults facilitated the oxidation of thiol groups of cysteine residues; human mutant SOD1 could generate
an upper shift band in reducing SDS-PAGE, which turned out to be a Cys111-peroxidized SOD1 species. We also detected the formation
of SOD1 multimers at different stages of the disease, and found that accumulated oxidative stress facilitated the formation
of aggregates, which were not mediated by disulfide bond. This oxidative modification of cysteine 111 therefore promotes the
formation of disulfide bond-independent aggregation of SOD1. 相似文献
997.
Sviridov AV Shushkova TV Zelenkova NF Vinokurova NG Morgunov IG Ermakova IT Leontievsky AA 《Applied microbiology and biotechnology》2012,93(2):787-796
Bacterial strains capable of utilizing methylphosphonic acid (MP) or glyphosate (GP) as the sole sources of phosphorus were
isolated from soils contaminated with these organophosphonates. The strains isolated from MP-contaminated soils grew on MP
and failed to grow on GP. One group of the isolates from GP-contaminated soils grew only on MP, while the other one grew on
MP and GP. Strains Achromobacter sp. MPS 12 (VKM B-2694), MP degraders group, and Ochrobactrum anthropi GPK 3 (VKM B-2554D), GP degraders group, demonstrated the best degradative capabilities towards MP and GP, respectively,
and were studied for the distribution of their organophosphonate catabolism systems. In Achromobacter sp. MPS 12, degradation of MP was catalyzed by C–P lyase incapable of degrading GP (C–P lyase I). Adaptation to growth on
GP yielded the strain Achromobacter sp. MPS 12A, which retained its ability to degrade MP via C–P lyase I and was capable of degrading GP with formation of sarcosine,
thus suggesting the involvement of a GP-specific C–P lyase II. O. anthropi GPK 3 also degraded MP via C–P lyase I, but degradation of GP in it was initiated by glyphosate oxidoreductase, which was
followed by product transformation via the phosphonatase pathway. 相似文献
998.
Christian E. Zimmerman Peter S. Rand Michio Fukushima Sergei F. Zolotukhin 《Environmental Biology of Fishes》2012,93(2):223-232
Sakhalin taimen (Parahucho perryi) range from the Russian Far East mainland along the Sea of Japan coast, and Sakhalin, Kuril, and Hokkaido Islands and are
considered to primarily be an anadromous species. We used otolith strontium-to-calcium ratios (Sr/Ca) to determine the chronology
of migration between freshwater and saltwater and identify migratory contingents of taimen collected from the Koppi River,
Russia. In addition, we examined taimen from the Sarufutsu River, Japan and Tumnin River, Russia that were captured in marine
waters. Transects of otolith Sr/Ca for the Sarufutsu River fish were consistent with patterns observed in anadromous salmonids.
Two fish from the Tumnin River appeared to be recent migrants to saltwater and one fish was characterized by an otolith Sr/Ca
transect consistent with marine migration. Using these transects as benchmarks, all Koppi River taimen were classified as
freshwater residents. These findings suggest more work is needed to assess life history variability among locations and the
role of freshwater productivity in controlling migratory behavior in taimen. 相似文献
999.
Nucifora LG Burke KA Feng X Arbez N Zhu S Miller J Yang G Ratovitski T Delannoy M Muchowski PJ Finkbeiner S Legleiter J Ross CA Poirier MA 《The Journal of biological chemistry》2012,287(19):16017-16028
Huntington disease is a genetic neurodegenerative disorder that arises from an expanded polyglutamine region in the N terminus of the HD gene product, huntingtin. Protein inclusions comprised of N-terminal fragments of mutant huntingtin are a characteristic feature of disease, though are likely to play a protective role rather than a causative one in neurodegeneration. Soluble oligomeric assemblies of huntingtin formed early in the aggregation process are candidate toxic species in HD. In the present study, we established an in vitro system to generate recombinant huntingtin in mammalian cells. Using both denaturing and native gel analysis, we have identified novel oligomeric forms of mammalian-derived expanded huntingtin exon-1 N-terminal fragment. These species are transient and were not previously detected using bacterially expressed exon-1 protein. Importantly, these species are recognized by 3B5H10, an antibody that recognizes a two-stranded hairpin conformation of expanded polyglutamine believed to be associated with a toxic form of huntingtin. Interestingly, comparable oligomeric species were not observed for expanded huntingtin shortstop, a 117-amino acid fragment of huntingtin shown previously in mammalian cell lines and transgenic mice, and here in primary cortical neurons, to be non-toxic. Further, we demonstrate that expanded huntingtin shortstop has a reduced ability to form amyloid-like fibrils characteristic of the aggregation pathway for toxic expanded polyglutamine proteins. Taken together, these data provide a possible candidate toxic species in HD. In addition, these studies demonstrate the fundamental differences in early aggregation events between mutant huntingtin exon-1 and shortstop proteins that may underlie the differences in toxicity. 相似文献
1000.