全文获取类型
收费全文 | 1574篇 |
免费 | 154篇 |
出版年
2023年 | 4篇 |
2022年 | 4篇 |
2021年 | 20篇 |
2020年 | 11篇 |
2019年 | 19篇 |
2018年 | 31篇 |
2017年 | 26篇 |
2016年 | 45篇 |
2015年 | 73篇 |
2014年 | 72篇 |
2013年 | 92篇 |
2012年 | 113篇 |
2011年 | 121篇 |
2010年 | 61篇 |
2009年 | 59篇 |
2008年 | 111篇 |
2007年 | 123篇 |
2006年 | 98篇 |
2005年 | 74篇 |
2004年 | 79篇 |
2003年 | 90篇 |
2002年 | 80篇 |
2001年 | 32篇 |
2000年 | 18篇 |
1999年 | 28篇 |
1998年 | 19篇 |
1997年 | 14篇 |
1996年 | 10篇 |
1995年 | 9篇 |
1994年 | 8篇 |
1993年 | 6篇 |
1992年 | 15篇 |
1991年 | 22篇 |
1990年 | 20篇 |
1989年 | 12篇 |
1988年 | 6篇 |
1987年 | 8篇 |
1986年 | 7篇 |
1985年 | 5篇 |
1984年 | 14篇 |
1983年 | 6篇 |
1982年 | 9篇 |
1981年 | 4篇 |
1980年 | 6篇 |
1979年 | 9篇 |
1978年 | 3篇 |
1977年 | 11篇 |
1976年 | 6篇 |
1975年 | 4篇 |
1973年 | 3篇 |
排序方式: 共有1728条查询结果,搜索用时 208 毫秒
1.
2.
M R Tremblay V Luu-The G Leblanc P No?l E Breton F Labrie D Poirier 《Bioorganic & medicinal chemistry》1999,7(6):1013-1023
The family of 17beta-hydroxysteroid dehydrogenases (17beta-HSDs) catalyzes the formation and inactivation of testosterone (T), dihydrotestosterone (DHT), and estradiol (E2), thus playing a crucial role in the regulation of active steroid hormones in target tissues. Among the five known 17beta-HSD enzymes, type II catalyzes the oxidation of E2 into estrone (E1), T into androstenedione, DHT into androstanedione, and 20alpha-dihydroprogesterone into progesterone. Specific inhibitors are thus an interesting means to study the regulation and to probe the structure of type II 17beta-HSD. In this context, we have efficiently synthesized a series of 7alpha-thioalkyl and 7alpha-thioaryl derivatives of spironolactone that inhibit type II 17beta-HSD. These new C19-steroidal inhibitors possess two important pharmacophores, namely 17-spiro-gamma-lactone and a bulky side-chain at the 7alpha-position. It was found that a para-substituted benzylthio group at the 7alpha-position enhances the inhibitory potency of spironolactone derivatives on type II 17beta-HSD. In fact, the compound with a para-hydroxy-benzylthio group showed an IC50 value of 0.5 microM against type II 17beta-HSD, whereas the compound with a para-[2-(1-piperidinyl)-ethoxy]-benzylthio group inhibited this enzyme with an IC50 value of 0.7 microM. The latter inhibitor is more selective than the former because it did not show any inhibitory potency against P450 aromatase as well as any affinity towards four steroid receptors (AR, PR, GR, ER). As a result, this inhibitor did not show any proliferative effect on androgen-sensitive Shionogi cells and estrogen-sensitive ZR-75-1 cells. These findings contribute to a better knowledge of the structure of type II 17beta-HSD and offer an interesting tool to study the regulation of this enzyme in several biological systems. 相似文献
3.
M Breton E Berrou E Deudon M C Brahimi-Horn J Picard 《Experimental cell research》1988,177(1):212-220
The effect of insulin upon proteoglycan synthesis was studied in cultured smooth muscle cells from pig aorta blocked in the G0 phase by serum deprivation. Insulin enhanced [35S]sulfate incorporation into cell layer and medium-secreted proteoglycans. The increase in incorporation of the precursor was not due to a mitogenic response by smooth muscle cells to the hormone and the specific radioactivity of proteoglycans showed that the stimulation reflected a real increase in sulfated proteoglycan synthesis. Maximal stimulation was observed, for the cell layer as well as for the medium, 40 h after the addition of 1.7 x 10(-7) M insulin and reached respectively 65 and 53%. This stimulation was about 80 and 60% of the level achieved with 10% fetal calf serum for cell layer and medium-secreted proteoglycans, respectively. The half-maximal effect was attained, for both the cell layer and the medium, in the presence of 2.1 x 10(-9) M insulin. Proteoglycans secreted into the medium, in the presence of 1.7 x 10(-8) M insulin for 40 h, showed a higher proportion of complexes (24%) than those synthesized in control medium (11%) and at least 95% of the monomers from culture treated with insulin were characterized by a smaller hydrodynamic size than those synthesized by cells maintained in control medium. This decrease in the size of proteoglycans was partly due to a decrease in the size of their glycanic chains. 相似文献
4.
S.C. Hung N.I. Ghali D.L. Venton G.C. Le Breton 《Prostaglandins & other lipid mediators》1982,24(2):195-206
The effects of prostaglandin F2α on human blood platelet function were investigated. PGF2α at 15 μM completely blocked platelet aggregation induced by 500 μM arachidonic acid or 3 μM U46619 but had no effect on aggregatin induced by 7.5 μM ADP. A similar specificity of action was not obtained with either PGI2 or PGE2. Thus concentrations of PGI2 (3 nM) or PGE2 (20 μ M) which inhibited U46619-induced aggregation by 100% also blocked ADP-stimulated aggregation.The inhibitory properties of PGF2α were not related to increases in platelet cAMP, since direct measurement of intracellular cAMP revealed that 15 μ M PGF2α produced no substantial change in cAMP levels. This finding was in direct contrast to results obtained using either PGI2 or PGE2. Both PGI2 (3 nM) and PGE2 (20 μ M) induced significant increases in platelet cAMP levels.The possibility that PGF2α directly interacts at the platelet TXA2/PGH2 receptor was investigated by measuring [3H]PGF2α binding to isolated platelet membranes. It was found that [3H] PGF2α binding reached equilibrium within 30 min at room temperature and could be 90% displaced by addition of 1000 fold excess of unlabelled PGF2α. Furthermore, when 1000 fold excess of either the TXA2/PGH2 “mimetic” U46619 or the TXA2/PGH2 antagonist 13-azaprostanoic acid was added, specific [3H] PGF2α binding was displaced by 95% and 85% respectively. In contrast, the same molar excess of 6-keto-PGF1α, azo analog 1, or TXB2, caused displacement of only 15%, 20% or 25% of the [3H] PGF2α binding. Scatchard analysis indicated that [3H] PGF2α has two binding sites; i.e., a high affinity binding site with an apparent Kd of 50 nM and a low affinity binding site with apparent Kd of 320 nM. These results suggest that the selective inhibition by PGF2α of AA or U46619-induced aggregation may be mediated through interaction at the platelet TXA2/PGH2 receptor. 相似文献
5.
Benjamin D. Jaffe Christelle Gudot Michael Ketterer Moh Leng Kok‐Yokomi Gary L. Leibee 《Ecological Entomology》2019,44(4):480-487
1. The consumption of arsenic is toxic to most biota. However, a noctuid caterpillar was recently reported feeding on a plant known to hyperaccumulate arsenic. 2. The aim of this study was to investigate the effects of arsenic‐rich Pteris vittata L. consumption by Callopistria floridensis G., and measure differences in arsenic concentrations at various stages of development (larval and adult), and associated with exuviae and frass. 3. Callopistria floridensis accumulated extraordinary concentrations of arsenic. The relative accumulation of arsenic was highest in exuviae and larvae. Larvae invariably preferred P. vittata grown on low arsenic soil to P. vittata grown on higher soil arsenic concentrations, and appeared able to selectively forage on lower arsenic concentrations within each treatment. 4. These findings show that C. floridensis is tolerant of arsenic, and successfully develops to adulthood containing elevated concentrations of arsenic. Callopistria floridensis represents the only known terrestrial animal capable of accumulating arsenic, and may have developed novel physiological and behavioural adaptations to regulate the negative effects of arsenic. 相似文献
6.
We have characterized a xanthophyll binding site, called V1, in the major light harvesting complex of photosystem II, distinct from the three tightly binding sites previously described as L1, L2, and N1. Xanthophyll binding to the V1 site can be preserved upon solubilization of the chloroplast membranes with the mild detergent dodecyl-alpha-d-maltoside, while an IEF purification step completely removes the ligand. Surprisingly, spectroscopic analysis showed that when bound in this site, xanthophylls are unable to transfer absorbed light energy to chlorophyll a. Pigments bound to sites L1, L2, and N1, in contrast, readily transfer energy to chlorophyll a. This result suggests that this binding site is not directly involved in light harvesting function. When violaxanthin, which in normal conditions is the main carotenoid in this site, is depleted by the de-epoxidation in strong light, the site binds other xanthophyll species, including newly synthesized zeaxanthin, which does not induce detectable changes in the properties of the complex. It is proposed that this xanthophyll binding site represents a reservoir of readily available violaxanthin for the operation of the xanthophyll cycle in excess light conditions. 相似文献
7.
8.
R. Breton M. Fiszman F. Gros 《Biochemical and biophysical research communications》1980,95(1):281-288
Proteins synthesized by cardiocytes isolated from 11d embryonic hearts and cultured have been compared with proteins present in the 11d embryonic heart. It is shown that cultured cardiocytes synthesize two new proteins, C1 and C2 with a molecular weight of 27 500 and pI of 6.35 and 6.05 respectively. The synthesis of these proteins is associated with the appearance of new RNA species. This induction is not related to the conditions of culture since it occurs with either aggregated cardioacytes grown in suspension or cardiocytes grown in monolayer. Finally no other embryonic cell types seem to synthesize these proteins. 相似文献
9.
The effect of global (15)N or (2)H labeling on the light-induced P700(+)/P700 FTIR difference spectra has been investigated in photosystem I samples from Synechocystis at 90 K. The small isotope-induced frequency shifts of the carbonyl modes observed in the P700(+)/P700 spectra are compared to those of isolated chlorophyll a. This comparison shows that bands at 1749 and 1733 cm(-)(1) and at 1697 and 1637 cm(-)(1), which upshift upon formation of P700(+), are candidates for the 10a-ester and 9-keto C=O groups of P700, respectively. A broad and relatively weak band peaking at 3300 cm(-)(1), which does not shift upon global labeling or (1)H-(2)H exchange, is ascribed to an electronic transition of P700(+), indicating that at least two chlorophyll a molecules (denoted P(1) and P(2)) participate in P700(+). Comparisons of the (3)P700/P700 FTIR difference spectrum at 90 K with spectra of triplet formation in isolated chlorophyll a or in RCs from photosystem II or purple bacteria identify the bands at 1733 and 1637 cm(-)(1), which downshift upon formation of (3)P700, as the 10a-ester and 9-keto C=O modes, respectively, of the half of P700 that bears the triplet (P(1)). Thus, while the P(2) carbonyls are free from interaction, both the 10a-ester and the 9-keto C=O of P(1) are hydrogen bonded and the latter group is drastically perturbed compared to chlorophyll a in solution. The Mg atoms of P(1) and P(2) appear to be five-coordinated. No localization of the triplet on the P(2) half of P700 is observed in the temperature range of 90-200 K. Upon P700 photooxidation, the 9-keto C=O bands of P(1) and P(2) upshift by almost the same amount, giving rise to the 1656(+)/1637(-) and 1717(+)/1697(-) cm(-)(1) differential signals, respectively. The relative amplitudes of these differential signals, as well as of those of the 10a-ester C=O modes, appear to be slightly dependent on sample orientation and temperature and on the organism used to generate the P700(+)/P700 spectrum. If it is assumed that the charge density on ring V of chlorophyll a, as measured by the perturbation of the 10a-ester or 9-keto C=O IR vibrations, mainly reflects the spin density on the two halves of the oxidized P700 special pair, a charge distribution ranging from 1:1 to 2:1 (in favor of P(2)) is deduced from the measurements presented here. The extreme downshift of the 9-keto C=O group of P(1), indicative of an unusually strong hydrogen bond, is discussed in relation with the models previously proposed for the PSI special pair. 相似文献
10.
The light-induced Fourier transform infrared (FTIR) difference spectra corresponding to the photoreduction of either the HA bacteriopheophytin electron acceptor (HA-/HA spectrum) or the QA primary quinone (QA-/QA spectrum) in photosynthetic reaction centers (RCs) of Rhodopseudomonas viridis are reported. These spectra have been compared for wild-type (WT) RCs and for two site-directed mutants in which the proposed interactions between the carbonyls on ring V of HA and the RC protein have been altered. In the mutant EQ(L104), the putative hydrogen bond between the protein and the 9-keto C=O of HA should be affected by changing Glu L104 to a Gln. In the mutant WF(M250), the van der Waals interactions between Trp M250 and the 10a-ester C=O of HA should be modified. The characteristic effects of both mutations on the FTIR spectra support the proposed interactions and allow the IR modes of the 9-keto and 10a-ester C=O of HA and HA- to be assigned. Comparison of the HA-/HA and QA-/QA spectra leads us to conclude that the QA-/QA IR signals in the spectral range above 1700 cm-1 are largely dominated by contributions from the electrostatic response of the 10a-ester C=O mode of HA upon QA photoreduction. A heterogeneity in the conformation of the 10a-ester C=O mode of HA in WT RCs, leading to three distinct populations of HA, appears to be related to differences in the hydrogen-bonding interactions between the carbonyls of ring V of HA and the RC protein. The possibility that this structural heterogeneity is related to the observed multiexponential kinetics of electron transfer and the implications for primary processes are discussed. The effect of 1H/2H exchange on the QA-/QA spectra of the WT and mutant RCs shows that neither Glu L104 nor any other exchangeable carboxylic residue changes appreciably its protonation state upon QA reduction. 相似文献