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991.
A series of 3-monohydroxylated bile acids, in unlabeled and radioactive form, of varying side chain length and configuration at C-3 has been synthesized and rigorously characterized. They include: 3 alpha- and 3 beta-hydroxy-5 beta-androstane-17 beta-carboxylic acids (C20); 3 alpha- and 3 beta-hydroxy-5 beta-pregnan-21-oic acids (C21); 3 alpha- and 3 beta-hydroxy-23,24-bisnor-5 beta-cholan-22-oic acids (C22); 3 alpha- and 3 beta-hydroxy-24-nor-5 beta-cholan-23-oic acids (C23, norlithocholic and isonorlithocholic acids); and 3 beta-hydroxy-5 beta-cholan-24-oic acid (C24, isolithocholic acid). A novel approach to the degradation of lithocholic acid acetate to 24-norlithocholic acid is described. This degradation involves the photochemical modification of a Hunsdiecker reaction and Kornblum oxidation of the intermediate 23-bromide. The availability of these compounds makes it possible to study the metabolism and biological effects of short chain bile acids. 相似文献
992.
Trinh Duong A E Ades Diana M Gibb Pat A Tookey Janet Masters 《BMJ (Clinical research ed.)》1999,319(7219):1227-1229
ObjectiveTo estimate and interpret time trends in vertical transmission rates for HIV using data from national obstetric and paediatric surveillance registers.DesignProspective study of HIV infected women reported through obstetric surveillance. HIV infection status of the child and onset of AIDS were reported through paediatric surveillance. Rates of vertical transmission and progression to AIDS rate were estimated by methods that take account of incomplete follow up of children with indeterminate infection status and delay in AIDS reporting.SettingBritish Isles.SubjectsPregnant women infected with HIV whose infection was diagnosed before delivery, and their babies.ResultsBy January 1999, 800 children born to diagnosed HIV infected women who had not breast fed had been reported. Vertical transmission rates rose to 19.6% (95% confidence interval 8.0% to 32.5%) in 1993 before falling to 2.2% (0% to 7.8%) in 1998. Between 1995 and 1998 use of antiretroviral treatment increased significantly each year, reaching 97% of live births in 1998. The rate of elective caesarean section remained constant, at around 40%, up to 1997 but increased to 62% in 1998. Caesarean section and antiretroviral treatment together were estimated to reduce risk of transmission from 31.6% (13.6% to 52.2%) to 4.2% (0.8% to 8.5%). The proportion of infected children developing AIDS in the first 6 months fell from 17.7% (6.8% to 30.8%) before 1994 to 7.2% (0% to 15.7%) after, coinciding with increased use of prophylaxis against Pneumocystis carinii pneumonia.ConclusionsIn the British Isles both HIV related morbidity and vertical transmission are being reduced through increased use of interventions.
Key messages
- Reliable estimates of HIV vertical transmission rates can be derived from surveillance data
- Infected pregnant women are increasingly taking up elective caesarean section and antiretroviral treatment to reduce the risk of transmitting HIV to their babies
- Vertical transmission rates have fallen greatly over the past four years and progression to AIDS among infected children may also have slowed
- These benefits can occur only if infected women are diagnosed before or during pregnancy
993.
994.
Lee HW Kim TI Chan KH Kwon MH Kim JS Jin M Kim YS 《Biochemical and biophysical research communications》2007,362(3):766-772
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), existing as homotrimer in solution, contains a unique zinc-binding site coordinated by three Cys230 residues at the tip of trimeric interface. TRAIL mutant with replacements of Cys230 with Ala (TRAIL(C230A)) negligibly formed trimeric structure and showed no apoptotic activity. Here, to elucidate the relationship between the trimeric stability and the apoptotic activity of TRAIL(C230A), we rationally designed mutations to induce homotrimerization of TRAIL(C230A) by substituting for the three residues involved in hydrogen bonding (Tyr183 and Tyr243) and putative repulsive electrostatic (Arg227) interactions at the buried trimeric interface into hydrophobic residues, like Y183F, Y243F, and R227I. The TRAIL(C230A)-derived mutants exhibited enhanced homotrimerization, but only the mutants containing R227I exhibited significant apoptosis-inducing activity in cancer cells. These results, together with the induction of rigid local structure around the zinc-binding region by R227I in TRAIL(C230A), suggest that ordered, rigid structure around the zinc-binding region is critical for the homotrimerization and apoptotic activity of TRAIL. 相似文献
995.
von Kleist-Retzow JC Hornig-Do HT Schauen M Eckertz S Dinh TA Stassen F Lottmann N Bust M Galunska B Wielckens K Hein W Beuth J Braun JM Fischer JH Ganitkevich VY Maniura-Weber K Wiesner RJ 《Experimental cell research》2007,313(14):3076-3089
Energy-producing pathways, adenine nucleotide levels, oxidative stress response and Ca(2+) homeostasis were investigated in cybrid cells incorporating two pathogenic mitochondrial DNA point mutations, 3243A>G and 3302A>G in tRNA(Leu(UUR)), as well as Rho(0) cells and compared to their parental 143B osteosarcoma cell line. All cells suffering from a severe respiratory chain deficiency were able to proliferate as fast as controls. The major defect in oxidative phosphorylation was efficiently compensated by a rise in anaerobic glycolysis, so that the total ATP production rate was preserved. This enhancement of glycolysis was enabled by a considerable decrease of cellular total adenine nucleotide pools and a concomitant shift in the AMP+ADP/ATP ratios, while the energy charge potential was still in the normal range. Further important consequences were an increased production of superoxide which, however, was neither escorted by major changes in the antioxidative defence systems nor was it leading to substantial oxidative damage. Most interestingly, the lowered mitochondrial membrane potential led to a disturbed intramitochondrial calcium homeostasis, which most likely is a major pathomechanism in mitochondrial diseases. 相似文献
996.
We studied three possible genotypes at 10 well-defined blood pressure (BP) QTLs using congenic rat lines. The central question was whether the hypertensive or normotensive allele is dominant, or whether there is partial dominance. The congenic strains were employed to investigate the BP effects of alleles originating from normotensive rats in the background of hypertensive Dahl salt-sensitive (DSS) rats. The normotensive alleles at eight QTLs were fully dominant over DSS alleles, which we tentatively interpreted as indicating that DSS rats incurred a loss of function at these loci and that the QTLs produced BP-reducing agents. In contrast, the normotensive allele of only one QTL was recessive over its DSS counterpart, implying a gain of function at this QTL or a null allele involved in generating a BP-elevating agent. Only one locus, C17QTL, had alleles exhibiting partial dominance. These estimates of dominance differ considerably from those obtained by QTL analysis in a F2 cross. This disagreement demonstrates the importance of establishing a cause-effect relationship between a QTL and its phenotypic effect via congenic strains. The dominance relationships suggest pertinent strategies for gene identification and pharmaceutical intervention. 相似文献
997.
Lloyd J Atwal KS Finlay HJ Nyman M Huynh T Bhandaru R Kover A Schmidt J Vaccaro W Conder ML Jenkins-West T Levesque P 《Bioorganic & medicinal chemistry letters》2007,17(12):3271-3275
K(V)1.5 blockers have the potential to be atrium-selective agents for treatment of atrial fibrillation. The benzopyrans provide a template for the synthesis of potent and selective K(V)1.5 blockers. 相似文献
998.
Nguyen Thi Xuan Nguyen Huy Hoang Vu Phuong Nhung Nguyen Thuy Duong Nguyen Hai Ha Nong Van Hai 《Journal of receptor and signal transduction research》2017,37(3):297-303
Insulin or insulin-like growth factor 1 (IGF-1) promotes the activation of phosphoinositide 3 kinase (PI3K)/Akt signaling in immune cells including dendritic cells (DCs), the most potent professional antigen-presenting cells for naive T cells. Klotho, an anti-aging protein, participates in the regulation of the PI3K/Akt signaling, thus the Ca2+-dependent migration is reduced in klotho-deficient DCs. The present study explored the effects of insulin/IGF-1 on DC function through klotho expression. To this end, the mouse bone marrow cells were isolated and cultured with GM-CSF to attain bone marrow-derived DCs (BMDCs). Cells were treated with insulin or IGF-1 and followed by stimulating with lipopolysaccharides (LPS). Tumor necrosis factor (TNF)-α formation was examined by enzyme-linked immunosorbent assay (ELISA). Phagocytosis was analyzed by FITC-dextran uptake assay. The expression of klotho was determined by quantitative PCR, immunoprecipitation and western blotting. As a result, treatment of the cells with insulin/IGF-1 resulted in reducing the klotho expression as well as LPS-stimulated TNF-α release and increasing the FITC-dextran uptake but unaltering reactive oxygen species (ROS) production in BMDCs. The effects were abolished by using pharmacological inhibition of PI3K/Akt with LY294002 and paralleled by transfecting DCs with klotho siRNA. In conclusion, the regulation of klotho sensitive DC function by IGF-1 or insulin is mediated through PI3K/Akt signaling pathway in BMDCs. 相似文献
999.
Genomic regions,cellular components and gene regulatory basis underlying pod length variations in cowpea (V. unguiculata L. Walp) 下载免费PDF全文
1000.
Nguyen Van Thang Vu Kim Thu Nguyen Xuan Nhiem Duong Thi Dung Tran Hong Quang Bui Huu Tai Hoang Le Tuan Anh Pham Hai Yen Nguyen Thi Thanh Ngan Nguyen Huy Hoang Phan Van Kiem 《化学与生物多样性》2017,14(5)
Five new oleanane‐type saponins, hirsutosides A – E, were isolated from the leaves of Glochidion hirsutum (Roxb .) Voigt . Their structures were elucidated as 21β‐benzoyloxy‐3β,16β,23,28‐tetrahydroxyolean‐12‐ene 3‐O‐β‐d ‐glucopyranoside ( 1 ), 21β‐benzoyloxy‐3β,16β,23,28‐tetrahydroxyolean‐12‐ene 3‐O‐β‐d ‐glucopyranosyl‐(1 → 3)‐β‐d ‐glucopyranoside ( 2 ), 21β‐benzoyloxy‐3β,16β,23,28‐tetrahydroxyolean‐12‐ene 3‐O‐6‐acetyl‐[β‐d ‐glucopyranosyl‐(1 → 3)]‐β‐d ‐glucopyranoside ( 3 ), 21β‐benzoyloxy‐3β,16β,23,28‐tetrahydroxyolean‐12‐ene 3‐O‐β‐d ‐glucopyranosyl‐(1 → 3)‐〈‐l ‐arabinopyranoside ( 4 ), and 21β‐benzoyloxy‐3β,16β,23‐trihydroxyolean‐12‐ene‐28‐al 3‐O‐β‐d ‐glucopyranosyl‐(1 → 3)‐α‐l ‐arabinopyranoside ( 5 ). All isolated compounds were evaluated for cytotoxic activities on four human cancer cell lines, HepG‐2, A‐549, MCF‐7, and SW‐626 using the SRB assay. Compounds 1 , 2 , 4 , and 5 showed significant cytotoxic activities against all human cancer cell lines with IC50 values ranging from 3.4 to 10.2 μm . Compound 3 containing acetyl group at glc C(6″) exhibited weak cytotoxic activity with IC50 values ranging from 47.0 to 54.4 μm . 相似文献