全文获取类型
收费全文 | 11173篇 |
免费 | 222篇 |
国内免费 | 211篇 |
专业分类
11606篇 |
出版年
2023年 | 165篇 |
2022年 | 209篇 |
2021年 | 286篇 |
2020年 | 356篇 |
2019年 | 594篇 |
2018年 | 487篇 |
2017年 | 354篇 |
2016年 | 291篇 |
2015年 | 155篇 |
2014年 | 716篇 |
2013年 | 1352篇 |
2012年 | 361篇 |
2011年 | 690篇 |
2010年 | 406篇 |
2009年 | 441篇 |
2008年 | 419篇 |
2007年 | 465篇 |
2006年 | 441篇 |
2005年 | 413篇 |
2004年 | 340篇 |
2003年 | 270篇 |
2002年 | 249篇 |
2001年 | 79篇 |
2000年 | 70篇 |
1999年 | 68篇 |
1998年 | 86篇 |
1997年 | 71篇 |
1996年 | 62篇 |
1995年 | 65篇 |
1994年 | 45篇 |
1993年 | 59篇 |
1992年 | 51篇 |
1991年 | 40篇 |
1990年 | 30篇 |
1989年 | 36篇 |
1988年 | 28篇 |
1986年 | 35篇 |
1985年 | 111篇 |
1984年 | 178篇 |
1983年 | 108篇 |
1982年 | 129篇 |
1981年 | 126篇 |
1980年 | 126篇 |
1979年 | 80篇 |
1978年 | 71篇 |
1977年 | 75篇 |
1976年 | 68篇 |
1975年 | 64篇 |
1974年 | 58篇 |
1973年 | 68篇 |
排序方式: 共有10000条查询结果,搜索用时 0 毫秒
91.
92.
Caspase-3:治疗神经退行性疾病的新靶点 总被引:9,自引:0,他引:9
Caspase-3是caspases家族(一类天冬氨酸特异性酶切半胱氨酸蛋白酶)中的成员,是哺乳动物细胞凋亡的关键蛋白酶.随着研究的深入,发现caspase-3在神经退行性疾病的病理过程中起着很重要的角色.Caspase-3在这些疾病的病理过程中,不仅仅是起着凋亡的效应器作用,还能直接与老年性痴呆症、帕金森氏症、亨廷顿舞蹈病、脊椎小脑失调等疾病的致病蛋白质分子相互作用,参与致病机制.因此,caspase-3是治疗神经退行性疾病的新靶点,寻找caspase-3高效高选择性的抑制剂将为治疗神经退行性疾病提供新的途径. 相似文献
93.
21-Hydroxypregna-l,4-diene-3,ll,20-trione was isolated from skate bile and as an in vivo metabolite of 3H-lα-hydroxycorticosterone. Identity was established by chromatography and derivatization to constant 3H/14C ratio and mass spectrometry of the 20,21-acetonide. The new steroid was present in the free form and as the glucuronoside. 相似文献
94.
Carina Proença Marisa Freitas Daniela Ribeiro Eduardo F. T. Oliveira Joana L. C. Sousa Sara M. Tomé 《Journal of enzyme inhibition and medicinal chemistry》2017,32(1):1216-1228
α-Glucosidase inhibitors are described as the most effective in reducing post-prandial hyperglycaemia (PPHG) from all available anti-diabetic drugs used in the management of type 2 diabetes mellitus. As flavonoids are promising modulators of this enzyme’s activity, a panel of 44 flavonoids, organised in five groups, was screened for their inhibitory activity of α-glucosidase, based on in vitro structure–activity relationship studies. Inhibitory kinetic analysis and molecular docking calculations were also applied for selected compounds. A flavonoid with two catechol groups in A- and B-rings, together with a 3-OH group at C-ring, was the most active, presenting an IC50 much lower than the one found for the most widely prescribed α-glucosidase inhibitor, acarbose. The present work suggests that several of the studied flavonoids have the potential to be used as alternatives for the regulation of PPHG. 相似文献
95.
菌株YS-K1是从镉污染土壤中筛选获得的一株耐镉马克思克鲁维酵母Kluyveromyces marxianus YS-K1,对其镉吸附特性研究结果表明,该菌对镉具有良好的耐受性和吸附性,即使在镉浓度高达140mg/L的培养基中也能生长,当镉浓度在30mg/L以下时,24h后能吸附溶液中90%以上的镉,且最佳吸附条件为pH6.0,温度30℃。该菌所吸附的镉大部分集中在细胞壁上,占总吸附镉的76%,细胞膜上的占9%,细胞质中的占15%;能量抑制剂2,4-二硝基苯酚(DNP)和二环己基碳二亚胺(DCC),分别能降低菌株15%和22%的镉吸附量。在Kluyveromyces marxianus YS-K1细胞中,锌离子与镉离子有共用的结合位点,锌离子不仅会与镉离子竞争细胞表面的结合位点,减少其对镉的吸附量,而且也会与镉离子竞争进入细胞的通道位点,减少其对镉的积累量,同时能部分恢复镉离子对菌株生长的抑制作用。 相似文献
96.
Speranskaya AS Krinitsina AA Revina TA Gerasimova NG Keruchen'ko YS Shevelev AB Valueva TA 《Biochemistry. Biokhimii?a》2006,71(11):1176-1182
The gene PKPI-B10 [AF536175] encoding in potato (Solanum tuberosum L., cv. Istrinskii) a Kunitz-type protein inhibitor of proteinases (PKPI) has been cloned into the pET23a vector and then expressed in Escherichia coli. The recombinant protein PKPI-B10 obtained as inclusion bodies was denatured, separated from admixtures by ion-exchange fast protein liquid chromatography (FPLC) on MonoQ under denaturing conditions, and renatured. The native protein was additionally purified by ion-exchange FPLC on DEAE-Toyopearl. The PKPI-B10 protein effectively inhibits the activity of trypsin, significantly weaker suppresses the activity of chymotrypsin, and has no effect on other serine proteinases: human leukocyte elastase, subtilisin Carlsberg, and proteinase K, and also the plant cysteine proteinase papain. 相似文献
97.
98.
Yu. E. Elisseeva E. V. Kugaevskaya 《Biochemistry (Moscow) Supplemental Series B: Biomedical Chemistry》2009,3(3):237-247
Somatic angiotensin converting enzyme (ACE) consists of two homologous catalytic domains (N- and C-domain), exhibiting different biochemical properties. The catalytically active ACE isoforms consisted of just one domain have been also detected in mammals. Substantial progress in ACE domain research was achieved during the last years, when their crystal structures were determined. The crystal structures of domains in complex with diverse potent ACE inhibitors provided new insights into structure-based differences of the domain active sites. Physiological functions of ACE are not limited by regulation of the cardiovascular system. Recent evidence suggests that the ACE domains may be also involved into control of different physiological functions. The C-terminal catalytic domain plays an important role in the regulation of blood pressure: it catalyzes angiotensin I cleavage in vivo. The N-domain contributes to the processing of other bioactive peptides for which it exhibits high affinity. The role of the N-domain is not ultimately associated with functioning of the rennin-angiotensin system and it contributes processing of other bioactive peptides for which it exhibits high affinity (goralatide, luliberin, enkephalin heptapeptide, beta-amyloid peptide). Domain-selective inhibitors selectively blocking either the N- or C-domain of ACE have been developed. 相似文献
99.
Combinatory responses of proinflamamtory cytokines have been examined on the nitric oxide-mediated function in cultured mouse calvarial osteoblasts. Interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) induced iNOS gene expression and NO production, although these actions were inhibited by L-NG-monomethylarginine (L-NMMA) and decreased alkaline phosphatase (ALPase) activity. Furthermore, NO donors, sodium nitroprusside (SNP) and NONOate dose-dependently elevated ALPase activity. In contrast, transforming-growth factor-β (TGF-β) decreased NO production stimulated by IL-1β, TNF-α and interferon-γ (IFN-γ). iNOS was expressed by mouse calvarial osteoblast cells after stimulation with IL-1β, TNF-α, and IFN-γ. Incubation of mouse calvarial osteoblast cells with the cytokines inhibited growth and ALPase activity. However, TGF-β-treatment abolished these effects of IL-1β, TNF-α and IFN-γ on growth inhibition and stimulation of ALPase in mouse calvarial osteoblast cells. In contrast, IL-1β, TNF-α, and IFN-γ exerted growth-inhibiting effects on mouse calvarial osteoblast cells which were partly NO-dependent. The results suggest that NO may act predominantly as a modulator of cytokine-induced effects on mouse calvarial osteoblast cells and TGF-β is a negative regulator of the NO production stimulated by IL-1β, TNF-α and IFN-γ. 相似文献
100.
Dae-Seok Kim Byeong-Gu Han Byung Il Lee Chang-Dae Bae 《Biochemical and biophysical research communications》2010,399(2):300-4790
Transglutaminase 2 (TGase2) is a calcium-dependent, cross-linking enzyme that catalyzes iso-peptide bond formation between peptide-bound lysine and glutamine residues. TGase 2 can activate NF-κB through the polymerization-mediated depletion of I-κBα without IKK activation. This NF-κB activation mechanism is associated with drug resistance in cancer cells. However, the polymers cannot be detected in cells, while TGase 2 over-expression depletes free I-κBα, which raises the question of how the polymerized I-κBα can be metabolized in cells. Among proteasome, lysosome and calpain systems, calpain inhibition was found to effectively increase the accumulation of I-κBα polymers in MCF7 cells transfected with TGase 2, and induced high levels of I-κBα polymers as well in MDA-MB-231 breast cancer cells that naturally express a high level of TGase 2. Inhibition of calpain also boosted the level of I-κBα polymers in HEK-293 cells in case of TGase 2 transfection either with I-κBα or I-κBα mutant (S32A, S36A). Interestingly, the combined inhibition of calpain and the proteasome resulted in an increased accumulation of both I-κBα polymers and I-κBα, concurrent with an inhibition of NF-κB activity in MDA-MB-231 cells. This suggests that μ-calpain proteasome-dependent I-κBα polymer degradation may contribute to cancer progression through constitutive NF-κB activation. 相似文献