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1.
Luigi Maierù 《Archive for History of Exact Sciences》1994,48(1):43-79
Summary Father Gesualdo Melacrinò (1725–1803), from Reggio Calabria (Italy), is an unknown Capuchin philosopher and theologian, who produced several works at the time he was teaching (only five years, from 1748–53); these works contained an original approach to the foundations and philosophy of mathematics. His main purpose was to reconciliate the classical traditions with the reality of his time. For him, this included a critical examination of the scholastic curriculum and a new orientation towards the methodological relevance of mathematics for all other sciences, especially for philosophy. Concerning mathematics, he emphasized the necessity of a basic revision and logical reconstruction of its foundations. This paper provides a comparative examination of Melacrinò's work with reference to its cultural and historical environment. 相似文献
2.
W. Rittel R. Maier M. Brugger B. Kamber B. Riniker P. Sieber 《Cellular and molecular life sciences : CMLS》1976,32(2):246-248
Summary Assays of 8 synthetic analogues of human calcitonin in rats showed that their hypocalcaemic activity was drastically reduced by deletion of the C-terminal amide group, chain-shortening or opening of the disulphide ring, but unaffected or enhanced by modification of the N-terminal amino group.
II. vgl.R. Maier, B. Kamber, B. Riniker andW. Rittel, Hormon. Metab. Res.7, 511 (1975).
Die hier verwendete, abgekürzte Schreibweise für Peptide folgt den Empfehlungen der IUPAC-IUB Kommission für Biochemische Nomenklatur, J.B.C.247, 977 (1972). Weitere Abkürzungen: HCT, Human-Calcitonin; PCT, Schweinecalcitonin; Bmp, -Mercaptopropionsäure (Desaminocystein); NMet, Normethionin (S-Methylcystein); -OMe, Methylester. 相似文献
II. vgl.R. Maier, B. Kamber, B. Riniker andW. Rittel, Hormon. Metab. Res.7, 511 (1975).
Die hier verwendete, abgekürzte Schreibweise für Peptide folgt den Empfehlungen der IUPAC-IUB Kommission für Biochemische Nomenklatur, J.B.C.247, 977 (1972). Weitere Abkürzungen: HCT, Human-Calcitonin; PCT, Schweinecalcitonin; Bmp, -Mercaptopropionsäure (Desaminocystein); NMet, Normethionin (S-Methylcystein); -OMe, Methylester. 相似文献
3.
Holst F Stahl PR Ruiz C Hellwinkel O Jehan Z Wendland M Lebeau A Terracciano L Al-Kuraya K Jänicke F Sauter G Simon R 《Nature genetics》2007,39(5):655-660
Using an Affymetrix 10K SNP array to screen for gene copy number changes in breast cancer, we detected a single-gene amplification of the ESR1 gene, which encodes estrogen receptor alpha, at 6q25. A subsequent tissue microarray analysis of more than 2,000 clinical breast cancer samples showed ESR1 amplification in 20.6% of breast cancers. Ninety-nine percent of tumors with ESR1 amplification showed estrogen receptor protein overexpression, compared with 66.6% cancers without ESR1 amplification (P < 0.0001). In 175 women who had received adjuvant tamoxifen monotherapy, survival was significantly longer for women with cancer with ESR1 amplification than for women with estrogen receptor-expressing cancers without ESR1 amplification (P = 0.023). Notably, we also found ESR1 amplification in benign and precancerous breast diseases, suggesting that ESR1 amplification may be a common mechanism in proliferative breast disease and a very early genetic alteration in a large subset of breast cancers. 相似文献
4.
Arianna Loregian Beatrice Mercorelli Giulio Nannetti Chiara Compagnin Giorgio Palù 《Cellular and molecular life sciences : CMLS》2014,71(19):3659-3683
Influenza viruses are major human pathogens responsible for respiratory diseases affecting millions of people worldwide and characterized by high morbidity and significant mortality. Influenza infections can be controlled by vaccination and antiviral drugs. However, vaccines need annual updating and give limited protection. Only two classes of drugs are currently approved for the treatment of influenza: M2 ion channel blockers and neuraminidase inhibitors. However, they are often associated with limited efficacy and adverse side effects. In addition, the currently available drugs suffer from rapid and extensive emergence of drug resistance. All this highlights the urgent need for developing new antiviral strategies with novel mechanisms of action and with reduced drug resistance potential. Several new classes of antiviral agents targeting viral replication mechanisms or cellular proteins/processes are under development. This review gives an overview of novel strategies targeting the virus and/or the host cell for counteracting influenza virus infection. 相似文献
5.
HIV-1 superinfection despite broad CD8+ T-cell responses containing replication of the primary virus 总被引:21,自引:0,他引:21
Altfeld M Allen TM Yu XG Johnston MN Agrawal D Korber BT Montefiori DC O'Connor DH Davis BT Lee PK Maier EL Harlow J Goulder PJ Brander C Rosenberg ES Walker BD 《Nature》2002,420(6914):434-439
Early treatment of acute HIV-1 infection followed by treatment interruptions has shown promise for enhancing immune control of infection. A subsequent loss of control, however, allows the correlates of protective immunity to be assessed. Here we show that sudden breakthrough of plasma viraemia occurred after prolonged immune containment in an individual infected with HIV-1 at a time when 25 distinct CD8+ T-cell epitopes in the viral proteins Gag, RT, Integrase, Env, Nef, Vpr, Vif and Rev were being targeted. Sequencing of the virus in plasma and cells showed that superinfection with a second clade-B virus was coincident with the loss of immune control. This sudden increase in viraemia was associated with a decline in half of the CD8+ T-cell responses. The declining CD8+ T-cell responses were coupled with sequence changes relative to the initial virus that resulted in impaired recognition. Our data show that HIV-1 superinfection can occur in the setting of a strong and broadly directed virus-specific CD8+ T-cell response. The lack of cross-protective immunity for closely related HIV-1 strains, despite persistent recognition of multiple CD8 epitopes, has important implications for public health and vaccine development. 相似文献
6.
Trigger factor in complex with the ribosome forms a molecular cradle for nascent proteins 总被引:1,自引:0,他引:1
During protein biosynthesis, nascent polypeptide chains that emerge from the ribosomal exit tunnel encounter ribosome-associated chaperones, which assist their folding to the native state. Here we present a 2.7 A crystal structure of Escherichia coli trigger factor, the best-characterized chaperone of this type, together with the structure of its ribosome-binding domain in complex with the Haloarcula marismortui large ribosomal subunit. Trigger factor adopts a unique conformation resembling a crouching dragon with separated domains forming the amino-terminal ribosome-binding 'tail', the peptidyl-prolyl isomerase 'head', the carboxy-terminal 'arms' and connecting regions building up the 'back'. From its attachment point on the ribosome, trigger factor projects the extended domains over the exit of the ribosomal tunnel, creating a protected folding space where nascent polypeptides may be shielded from proteases and aggregation. This study sheds new light on our understanding of co-translational protein folding, and suggests an unexpected mechanism of action for ribosome-associated chaperones. 相似文献
7.
Instrumental observations and reconstructions of global and hemispheric temperature evolution reveal a pronounced warming during the past approximately 150 years. One expression of this warming is the observed increase in the occurrence of heatwaves. Conceptually this increase is understood as a shift of the statistical distribution towards warmer temperatures, while changes in the width of the distribution are often considered small. Here we show that this framework fails to explain the record-breaking central European summer temperatures in 2003, although it is consistent with observations from previous years. We find that an event like that of summer 2003 is statistically extremely unlikely, even when the observed warming is taken into account. We propose that a regime with an increased variability of temperatures (in addition to increases in mean temperature) may be able to account for summer 2003. To test this proposal, we simulate possible future European climate with a regional climate model in a scenario with increased atmospheric greenhouse-gas concentrations, and find that temperature variability increases by up to 100%, with maximum changes in central and eastern Europe. 相似文献
8.
Soil fertility limits carbon sequestration by forest ecosystems in a CO2-enriched atmosphere 总被引:15,自引:0,他引:15
Oren R Ellsworth DS Johnsen KH Phillips N Ewers BE Maier C Schäfer KV McCarthy H Hendrey G McNulty SG Katul GG 《Nature》2001,411(6836):469-472
Northern mid-latitude forests are a large terrestrial carbon sink. Ignoring nutrient limitations, large increases in carbon sequestration from carbon dioxide (CO2) fertilization are expected in these forests. Yet, forests are usually relegated to sites of moderate to poor fertility, where tree growth is often limited by nutrient supply, in particular nitrogen. Here we present evidence that estimates of increases in carbon sequestration of forests, which is expected to partially compensate for increasing CO2 in the atmosphere, are unduly optimistic. In two forest experiments on maturing pines exposed to elevated atmospheric CO2, the CO2-induced biomass carbon increment without added nutrients was undetectable at a nutritionally poor site, and the stimulation at a nutritionally moderate site was transient, stabilizing at a marginal gain after three years. However, a large synergistic gain from higher CO2 and nutrients was detected with nutrients added. This gain was even larger at the poor site (threefold higher than the expected additive effect) than at the moderate site (twofold higher). Thus, fertility can restrain the response of wood carbon sequestration to increased atmospheric CO2. Assessment of future carbon sequestration should consider the limitations imposed by soil fertility, as well as interactions with nitrogen deposition. 相似文献
9.
10.