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941.
Wilen CB Wang J Tilton JC Miller JC Kim KA Rebar EJ Sherrill-Mix SA Patro SC Secreto AJ Jordan AP Lee G Kahn J Aye PP Bunnell BA Lackner AA Hoxie JA Danet-Desnoyers GA Bushman FD Riley JL Gregory PD June CH Holmes MC Doms RW 《PLoS pathogens》2011,7(4):e1002020
HIV-1 entry requires the cell surface expression of CD4 and either the CCR5 or CXCR4 coreceptors on host cells. Individuals homozygous for the ccr5Δ32 polymorphism do not express CCR5 and are protected from infection by CCR5-tropic (R5) virus strains. As an approach to inactivating CCR5, we introduced CCR5-specific zinc-finger nucleases into human CD4+ T cells prior to adoptive transfer, but the need to protect cells from virus strains that use CXCR4 (X4) in place of or in addition to CCR5 (R5X4) remains. Here we describe engineering a pair of zinc finger nucleases that, when introduced into human T cells, efficiently disrupt cxcr4 by cleavage and error-prone non-homologous DNA end-joining. The resulting cells proliferated normally and were resistant to infection by X4-tropic HIV-1 strains. CXCR4 could also be inactivated in ccr5Δ32 CD4+ T cells, and we show that such cells were resistant to all strains of HIV-1 tested. Loss of CXCR4 also provided protection from X4 HIV-1 in a humanized mouse model, though this protection was lost over time due to the emergence of R5-tropic viral mutants. These data suggest that CXCR4-specific ZFNs may prove useful in establishing resistance to CXCR4-tropic HIV for autologous transplant in HIV-infected individuals. 相似文献
942.
ADP regulates SNF1, the Saccharomyces cerevisiae homolog of AMP-activated protein kinase 总被引:1,自引:0,他引:1
Mayer FV Heath R Underwood E Sanders MJ Carmena D McCartney RR Leiper FC Xiao B Jing C Walker PA Haire LF Ogrodowicz R Martin SR Schmidt MC Gamblin SJ Carling D 《Cell metabolism》2011,14(5):707-714
The SNF1 protein kinase complex plays an essential role in regulating gene expression in response to the level of extracellular glucose in budding yeast. SNF1 shares structural and functional similarities with mammalian AMP-activated protein kinase. Both kinases are activated by phosphorylation on a threonine residue within the activation loop segment of the catalytic subunit. Here we show that ADP is the long-sought metabolite that activates SNF1 in response to glucose limitation by protecting the enzyme against dephosphorylation by Glc7, its physiologically relevant protein phosphatase. We also show that the regulatory subunit of SNF1 has two ADP binding sites. The tighter site binds AMP, ADP, and ATP competitively with NADH, whereas the weaker site does not bind NADH, but is responsible for mediating the protective effect of ADP on dephosphorylation. Mutagenesis experiments suggest that the general mechanism by which ADP protects against dephosphorylation is strongly conserved between SNF1 and AMPK. 相似文献
943.
Kim MJ Kim CS Park JY Park SN Yoo SY Lee SY Kook JK 《Journal of microbiology (Seoul, Korea)》2011,49(1):165-168
In general, an antimicrobial test for screening anti-caries natural extracts was performed by measuring the minimum bactericidal
concentration (MBC) against the type strains of mutans streptococci. However, it is unclear if the antimicrobial efficiency
of natural extracts on the type strains of mutans streptococci is the same on the clinical strains. In this study, we introduced
a bacterial model system for the screening of anti-caries and determining the optimal concentration of them to develop oral
hygiene products for Korean populations. 相似文献
944.
Perin EC Tian M Marini FC Silva GV Zheng Y Baimbridge F Quan X Fernandes MR Gahremanpour A Young D Paolillo V Mukhopadhyay U Borne AT Uthamanthil R Brammer D Jackson J Decker WK Najjar AM Thomas MW Volgin A Rabinovich B Soghomonyan S Jeong HJ Rios JM Steiner D Robinson S Mawlawi O Pan T Stafford J Kundra V Li C Alauddin MM Willerson JT Shpall E Gelovani JG 《PloS one》2011,6(9):e22949
The long-term fate of stem cells after intramyocardial delivery is unknown. We used noninvasive, repetitive PET/CT imaging with [(18)F]FEAU to monitor the long-term (up to 5 months) spatial-temporal dynamics of MSCs retrovirally transduced with the sr39HSV1-tk gene (sr39HSV1-tk-MSC) and implanted intramyocardially in pigs with induced acute myocardial infarction. Repetitive [(18)F]FEAU PET/CT revealed a biphasic pattern of sr39HSV1-tk-MSC dynamics; cell proliferation peaked at 33-35 days after injection, in periinfarct regions and the major cardiac lymphatic vessels and lymph nodes. The sr39HSV1-tk-MSC-associated [(18)F]FEAU signals gradually decreased thereafter. Cardiac lymphography studies using PG-Gd-NIRF813 contrast for MRI and near-infrared fluorescence imaging showed rapid clearance of the contrast from the site of intramyocardial injection through the subepicardial lymphatic network into the lymphatic vessels and periaortic lymph nodes. Immunohistochemical analysis of cardiac tissue obtained at 35 and 150 days demonstrated several types of sr39HSV1-tk expressing cells, including fibro-myoblasts, lymphovascular cells, and microvascular and arterial endothelium. In summary, this study demonstrated the feasibility and sensitivity of [(18)F]FEAU PET/CT imaging for long-term, in-vivo monitoring (up to 5 months) of the fate of intramyocardially injected sr39HSV1-tk-MSC cells. Intramyocardially transplanted MSCs appear to integrate into the lymphatic endothelium and may help improve myocardial lymphatic system function after MI. 相似文献
945.
Liang RM Yong XL Jiang YP Tan YH Dai BD Wang SH Hu TT Chen X Li N Dong ZH Huang XC Chen J Cao YB Jiang YY 《The FEBS journal》2011,278(7):1075-1085
Candida infections have become an increasingly significant problem, mainly because of the widespread nature of Candida and drug resistance. There is an urgent need to develop new classes of drugs for the treatment of opportunistic Candida infections, especially in medically complex patients. Previous studies have confirmed that 2-amino-nonyl-6-methoxyl-tetralin muriate (10b) possesses powerful antifungal activity in vitro against Candia albicans. To clarify the underlying action mechanism, an oligonucleotide microarray study was performed in C. albicans SC5314 without and with 10b treatment. The analytical results showed that energy metabolism-related genes, including glycolysis-related genes (PFK1, CDC19 and HXK2), fermentation-related genes (PDC11, ALD5 and ADH1) and respiratory electron transport chain-related genes (CBP3, COR1 and QCR8), were downregulated significantly. Functional analysis revealed that 10b treatment increased the generation of endogenous reactive oxygen species, and decreased mitochondrial membrane potential, ubiquinone-cytochrome c reductase (complex III) activity and intracellular ATP levels in C. albicans SC5314. Also, addition of the antioxidant ascorbic acid reduced the antifungal activity of 10b significantly. These results suggest that mitochondrial aerobic respiration shift and endogenous reactive oxygen species augmentation might contribute to the antifungal activity of 10b against C. albicans. This information may prove to be useful for the development of new strategies to treat Candida infections. 相似文献
946.
Background and Objectives
Tumor necrosis factor-α (TNF-α) plays a very important role in the development and progress of cancer. Some TNF-α polymorphisms have been confirmed to increase cancer risks; however, the association between TNF-α-238 polymorphism and cancers remains controversial and ambiguous. The aim of this study is to explore a more precise estimation of its relationship with cancer using meta-analysis.Methods
Electronic searches of several databases were conducted for all publications on the association between this variant and cancer through March 2011. Odds ratios (OR) with 95% confidence intervals (95% CI) were used to access the strength of this association in the random-effect model.Results
Thirty four studies with 34,679 cancer patients and 41,186 healthy controls were included. This meta-analysis showed no significant association between TNF-α-238 polymorphism and cancers (AA+GA vs GG: OR = 1.09, 95%CI = 0.88–1.34). In Caucasian and Asian subgroups, OR values (95% CI) were 1.14 (0.91–1.43) and 0.97 (0.58–1.61), respectively. In the subgroups of cancer type, no significant association was detected. The sensitivity analysis further strengthened the validity of these negative associations. No publication bias was observed in this study.Conclusions
No significant association was found between the TNF-α-238 polymorphism and the risk for cancer. 相似文献947.
948.
Chun Zhang Qi Li La Zhu Wangchao He Conghui Yang Hui Zhang Yu Sun Luojing Zhou Yuandong Sun Shurun Zhu Chang Wu Min Tao Yi Zhou Rurong Zhao Chenchen Tang Shaojun Liu 《中国科学:生命科学英文版》2021,(11):1917-1928
Meiosis is the key process for producing mature gametes.A natural fertile triploid Carassius auratus population (3nDTCC) and an artificially derived sterile tri... 相似文献
949.
950.
Toshiyuki Imasawa Kentaro Koike Jerold Chun 《Biochemical and biophysical research communications》2010,392(2):207-211
Sphingosine 1-phosphate (S1P) is a potent sphingolipid mediator that acts through five cognate G protein-coupled receptors (S1P1-S1P5) and regulates many critical biological processes. Recent studies indicated that S1P at nanomolar concentrations significantly reduces cytokine-induced apoptosis of pancreatic β-cells in which genes for S1P1-S1P4 are co-expressed. However, the S1P receptor subtype(s) involved in this effect remains to be clarified. In this study, we investigated the potential role of S1P2 in streptozotocin (STZ)-induced apoptosis of pancreatic β-cells and progression of diabetes. S1P2-deficient (S1P2-/-) mice displayed a greater survive ability, lower blood glucose levels, and smaller numbers of TUNEL-positive apoptotic β-cells to administration of a high dose of STZ than wild-type (WT) mice. S1P2-/- mice showed higher insulin/glucose ratios (an index of relative insulin deficiency) and larger insulin-positive islet areas to administration of a low dose of STZ than WT mice. Moreover, administration of JTE-013, a S1P2-specific antagonist, to WT mice ameliorated STZ-induced blood glucose elevation and reduced the incidence of diabetes. Our findings indicate that blockade of S1P2 signaling attenuates STZ-induced apoptosis of pancreatic β-cells and decreases the incidence of diabetes. 相似文献