全文获取类型
收费全文 | 6608篇 |
免费 | 605篇 |
国内免费 | 648篇 |
专业分类
7861篇 |
出版年
2024年 | 20篇 |
2023年 | 148篇 |
2022年 | 176篇 |
2021年 | 208篇 |
2020年 | 221篇 |
2019年 | 262篇 |
2018年 | 246篇 |
2017年 | 262篇 |
2016年 | 221篇 |
2015年 | 236篇 |
2014年 | 273篇 |
2013年 | 526篇 |
2012年 | 214篇 |
2011年 | 321篇 |
2010年 | 249篇 |
2009年 | 366篇 |
2008年 | 339篇 |
2007年 | 372篇 |
2006年 | 326篇 |
2005年 | 317篇 |
2004年 | 265篇 |
2003年 | 257篇 |
2002年 | 209篇 |
2001年 | 163篇 |
2000年 | 141篇 |
1999年 | 150篇 |
1998年 | 137篇 |
1997年 | 108篇 |
1996年 | 118篇 |
1995年 | 94篇 |
1994年 | 92篇 |
1993年 | 79篇 |
1992年 | 83篇 |
1991年 | 80篇 |
1990年 | 59篇 |
1989年 | 48篇 |
1988年 | 33篇 |
1987年 | 53篇 |
1986年 | 37篇 |
1985年 | 50篇 |
1984年 | 53篇 |
1983年 | 36篇 |
1982年 | 47篇 |
1981年 | 27篇 |
1980年 | 21篇 |
1979年 | 27篇 |
1978年 | 18篇 |
1977年 | 26篇 |
1976年 | 17篇 |
1975年 | 12篇 |
排序方式: 共有7861条查询结果,搜索用时 0 毫秒
1.
David R. Nelson 《Philosophical transactions of the Royal Society of London. Series B, Biological sciences》2013,368(1612)
The world we live in is a biosphere influenced by all organisms who inhabit it. It is also an ecology of genes, with some having rather startling effects. The premise put forth in this issue is cytochrome P450 is a significant player in the world around us. Life and the Earth itself would be visibly different and diminished without cytochrome P450s. The contributions to this issue range from evolution on the billion year scale to the colour of roses, from Darwin to Rachel Carson; all as seen through the lens of cytochrome P450. 相似文献
2.
R. Balabsubramanian G. Raghunathan 《International journal of biological macromolecules》1982,4(6):377-378
The distribution of regular secondary structures, viz. α-helices and β-strands, along the length of over 70 properties whose secondary structural details have been reported, has been analysed. The occurrence of these regular structures tends to be a maximum at the N- and C-termini. Our analysis suggests that both these free ends could possibly serve as nucleating centers for secondary structures and could play an important role in the folding of proteins. 相似文献
3.
A review of in vitro mutagenesis assessment of metal compounds in mammalian and nonmammalian test systems has been compiled.
Prokaryotic assays are ineffective or inconsistent in their detection of most metals as mutagens, with the notable exception
of hexavalent chromium. Mammalian assay systems appear to be similarly inappropriate for the screening of metal compounds
based upon the limited number of studies that have employed those compounds having known carcinogenic activity. Although of
limited value as screening tests for the detection of potentially carcinogenic metal compounds, the well-characterized in
vitro mutagenesis systems may prove to be of significant value as a means to elucidate mechanisms of metal genotoxicity. 相似文献
4.
《Bioorganic & medicinal chemistry》2016,24(4):886-893
In order to search for novel multifunctional anti-Alzheimer agents, a series of ferulic acid–carbazole hybrid compounds were designed and synthesized. Ellman’s assay revealed that the hybrid compounds showed moderate to potent inhibitory activity against the cholinesterases. Particularly, the AChE inhibition potency of compound 5k (IC50 1.9 μM) was even 5-fold higher than that of galantamine. In addition, the target compounds showed pronounced antioxidant ability and neuroprotective property, especially against the ROS-induced toxicity. Notably, the neuroprotective effect of 5k was obviously superior to that of the mixture of ferulic acid and carbazole, indicating the therapeutic effect of the hybrid compound is better than the combination administration of the corresponding mixture. 相似文献
5.
《Bioorganic & medicinal chemistry》2019,27(12):2340-2344
A synthetic flavone derivative 2-(benzo[d][1,3]dioxol-5-yl)-4H-chromen-4-one (BDC) was synthesized by the one pot reaction method and assessed for α-glucosidase inhibitory activity. The BDC demonstrated dose dependent inhibition of α-glucosidase activity. A maximum inhibition (99.3 ± 0.26%) of α-glucosidase was observed at 27.6 µM. The maximum α-glucosidase inhibitory activity depicted by BDC 27.6 µM concentration was 22.4 fold over the maximum inhibition observed with acarbose (97.72 ± 0.59% at 669.57 µM), a standard commercial anti-diabetic drug. In contrast to acarbose that depicted competitive type inhibition, kinetic studies of α-glucosidase inhibition by BDC demonstrated non-competitive inhibition with Km of 0.71 mM−1 and a Vmax of 0.028 mmol/min. In silico studies suggest allosteric interaction of BDC with α-glucosidase at a minimum binding energy (ΔG) of −8.64 kcal/mol and Ki of 465.3 nM, whereas, acarbose interacted at the active site of α-glucosidase with ΔG of −9.23 kcal/mol and Ki of 172 nM. Thus BDC significantly inhibited α-glucosidase in comparison to acarbose. Moreover, BDC has been endorsed for drug likeness by evaluating it as per Lipinski rule of five. Thus, BDC can be a lead compound for the management of type-2 diabetes mellitus. 相似文献
6.
Lawrence Que Jr. 《Journal of biological inorganic chemistry》2004,9(6):684-690
The oxygen activation mechanisms proposed for nonheme iron systems generally follow the heme paradigm in invoking the involvement of iron-peroxo and iron-oxo species in their catalytic cycles. However, the nonheme ligand environments allow for end-on and side-on dioxygen coordination and impart greater flexibility in the modes of dioxygen activation. The currently available evidence for nonheme iron-peroxo and iron-oxo intermediates is summarized and discussed in light of the ongoing discussion on the nature of the oxidant(s) in heme enzymes. 相似文献
7.
Kiyohiko Sugano 《化学与生物多样性》2009,6(11):2014-2029
Bile micelles play an important role in oral absorption of low‐solubility compounds. Bile micelles can affect solubility, dissolution rate, and permeability. For the pH–solubility profile in bile micelles, the Henderson–Hasselbalch equation should be modified to take bile‐micelle partition into account. For the dissolution rate, in the Nernst–Brunner equation, the effective diffusion coefficient in bile‐micelle media should be used instead of the monomer diffusion coefficient. The diffusion coefficient of bile micelles is 8‐ to 18‐fold smaller than that of monomer molecules. For permeability, the effective diffusion coefficient in the unstirred water layer adjacent to the epithelial membrane, and the free fraction at the epithelial membrane surface should be taken into account. The importance of these aspects is demonstrated here using several in vivo and clinical oral‐absorption data of low‐solubility model compounds. Using the theoretical equations, the food effect on oral absorption is further discussed. 相似文献
8.
1. The effects of a moderate addition of nutrients (twofold N and threefold P) were examined during a 2‐year period to determine the response to nutrient addition in a meiofaunal community inhabiting sandy patches in a Mediterranean stream. 2. The pattern of meiofaunal assemblages exhibits a high degree of intra‐ and interannual variability. This pattern alternates between periods of hydrological stability and disturbances, such as floods and droughts, which is a characteristic of Mediterranean systems. 3. A before–after–control–impact (BACI) design was used to determine the outcome of the addition by comparing an upstream non‐enriched reach with an enriched downstream reach. Analysis of the study data by means of a nonparametric permutational procedure (permanova ) showed that fertilisation had a significant effect. Density and biomass values increased in the most abundant meiofaunal groups, including microcrustaceans, oligochaetes and chironomids. Microcrustaceans were the dominant group in the permanent meiofauna. 4. We also examined differences in microcrustacean secondary production in both reaches. Ostracods and cyclopoid copepods increased their secondary production in the impacted reach as a result of the nutrient addition. 5. Our study demonstrated that moderate nutrient enrichment can affect the biomass and production of stream meiofauna, but it is still unclear whether this effect was because of autotrophic or heterotrophic pathways. 相似文献
9.
S Braig R M Wiedmann J Liebl M Singer R Kubisch L Schreiner B A Abhari E Wagner U Kazmaier S Fulda A M Vollmar 《Cell death & disease》2014,5(1):e1001
Tubulin-binding agents such as taxol, vincristine or vinblastine are well-established drugs in clinical treatment of metastatic cancer. However, because of their highly complex chemical structures, the synthesis and hence the supply issues are still quite challenging. Here we set on stage pretubulysin, a chemically accessible precursor of tubulysin that was identified as a potent microtubule-binding agent produced by myxobacteria. Although much simpler in chemical structure, pretubulysin abrogates proliferation and long-term survival as well as anchorage-independent growth, and also induces anoikis and apoptosis in invasive tumor cells equally potent to tubulysin. Moreover, pretubulysin posseses in vivo efficacy shown in a chicken chorioallantoic membrane (CAM) model with T24 bladder tumor cells, in a mouse xenograft model using MDA-MB-231 mammary cancer cells and finally in a model of lung metastasis induced by 4T1 mouse breast cancer cells. Pretubulysin induces cell death via the intrinsic apoptosis pathway by abrogating the expression of pivotal antiapoptotic proteins, namely Mcl-1 and Bcl-xL, and shows distinct chemosensitizing properties in combination with TRAIL in two- and three-dimensional cell culture models. Unraveling the underlying signaling pathways provides novel information: pretubulysin induces proteasomal degradation of Mcl-1 by activation of mitogen-activated protein kinase (especially JNK (c-Jun N-terminal kinase)) and phosphorylation of Mcl-1, which is then targeted by the SCFFbw7 E3 ubiquitin ligase complex for ubiquitination and degradation. In sum, we designate the microtubule-destabilizing compound pretubulysin as a highly promising novel agent for mono treatment and combinatory treatment of invasive cancer. 相似文献
10.