全文获取类型
收费全文 | 4140篇 |
免费 | 235篇 |
专业分类
4375篇 |
出版年
2023年 | 16篇 |
2022年 | 51篇 |
2021年 | 53篇 |
2020年 | 33篇 |
2019年 | 67篇 |
2018年 | 88篇 |
2017年 | 70篇 |
2016年 | 98篇 |
2015年 | 157篇 |
2014年 | 177篇 |
2013年 | 330篇 |
2012年 | 285篇 |
2011年 | 295篇 |
2010年 | 173篇 |
2009年 | 166篇 |
2008年 | 250篇 |
2007年 | 214篇 |
2006年 | 218篇 |
2005年 | 177篇 |
2004年 | 167篇 |
2003年 | 166篇 |
2002年 | 138篇 |
2001年 | 75篇 |
2000年 | 80篇 |
1999年 | 60篇 |
1998年 | 37篇 |
1997年 | 42篇 |
1996年 | 38篇 |
1995年 | 36篇 |
1994年 | 29篇 |
1993年 | 34篇 |
1992年 | 51篇 |
1991年 | 45篇 |
1990年 | 49篇 |
1989年 | 39篇 |
1988年 | 49篇 |
1987年 | 26篇 |
1986年 | 20篇 |
1985年 | 39篇 |
1984年 | 21篇 |
1983年 | 18篇 |
1982年 | 17篇 |
1981年 | 19篇 |
1980年 | 12篇 |
1979年 | 19篇 |
1978年 | 30篇 |
1977年 | 16篇 |
1976年 | 18篇 |
1975年 | 9篇 |
1966年 | 9篇 |
排序方式: 共有4375条查询结果,搜索用时 15 毫秒
51.
A glucosyl group from uridine diphosphate [U-14C]glucose is incorporated into a phosphoglycolipid, probably a glucosylphosphatidylglycerol, by a disrupted membrane enzyme preparation from a gram-negative, moderately halophilic bacterium, Pseudomonas halosaccharolytica ATCC 29423. The conversion of [14C]phosphatidylglycerol into phosphoglycolipid by the particulate preparation was also enhanced in the presence of non-labelled UDP-glucose. A chemical degradation study of labelled phosphoglycolipid showed the bulk of the radioactivity from UDP[U-14C]glucose to be associated with the glucose moiety, which also appeared to be attached to the hydroxyl group of a second glycerol. 相似文献
52.
In order to investigate how changes in the structures of side-chain aromatic groups of specific substrates influence binding and kinetic specificity in alpha chymotrypsin [EC 3.4.21.1]-catalyzed reactions, a number of nucleus-substituted derivatives of the specific ester substrates were prepared and steady-state kinetic studies were carried out at pH 6.5 and 7.8. Ac-Trp(NCps)-OMe was hydrolyzed more readily at low substrate concentration than Ac-Trp-OMe due to its smaller Km(app) value, suggesting that the bulky 2-nitro-4-carboxyphenylsulfenyl moiety interacts with outer residues rather than with those in the hydrophobic pocket and that this interaction increases the binding specificity. Inhibition experiments using the corresponding carboxylate and analogous inhibitors, however, showed that the carboxy group at the para position of the phenyl nucleus of the substituent sterically hinders association with the active site of alpha-chymotrypsin at pH 7.8 but not at pH 6.5. The kcat values of Ac-Trp(CHO)-0Me, Ac-Tyr(3-NO2)-OMe, and Ac-m-Tyr-OMe were much higher than those of the corresponding specific substrates, indicating that derivatives with a substitute as large as a formyl, nitro or hydroxyl group at the xi-position are stereochemically favorable to the catalytic process. Remarkable increases in Km(app) were also observed. The individual parameters for Ac-Dopa-OMe, however, were comparable to those for Ac-Tyr-OMe. 相似文献
53.
Ayaka Komatsu Izumi Iida Yusuke Nasu Genki Ito Fumiko Harada Sari Kishikawa Stephen J. Moss Takeyasu Maeda Miho Terunuma 《The Journal of biological chemistry》2022,298(5)
Hyperammonemia is known to cause various neurological dysfunctions such as seizures and cognitive impairment. Several studies have suggested that hyperammonemia may also be linked to the development of Alzheimer’s disease (AD). However, the direct evidence for a role of ammonia in the pathophysiology of AD remains to be discovered. Herein, we report that hyperammonemia increases the amount of mature amyloid precursor protein (mAPP) in astrocytes, the largest and most prevalent type of glial cells in the central nervous system that are capable of metabolizing glutamate and ammonia, and promotes amyloid beta (Aβ) production. We demonstrate the accumulation of mAPP in astrocytes was primarily due to enhanced endocytosis of mAPP from the plasma membrane. A large proportion of internalized mAPP was targeted not to the lysosome, but to the endoplasmic reticulum, where processing enzymes β-secretase BACE1 (beta-site APP cleaving enzyme 1) and γ-secretase presenilin-1 are expressed, and mAPP is cleaved to produce Aβ. Finally, we show the ammonia-induced production of Aβ in astrocytic endoplasmic reticulum was specific to Aβ42, a principal component of senile plaques in AD patients. Our studies uncover a novel mechanism of Aβ42 production in astrocytes and also provide the first evidence that ammonia induces the pathogenesis of AD by regulating astrocyte function. 相似文献
54.
55.
Ohno F Watanabe J Sekihara H Hirabayashi T Arata S Kikuyama S Shioda S Nakaya K Nakajo S 《Regulatory peptides》2005,126(1-2):115-122
We have found that pituitary adenylate cyclase-activating polypeptide (PACAP) employed at the physiological concentrations induces the differentiation of mouse neural stem cells into astrocytes. The differentiation process was not affected by cAMP analogues such as dibutylic cAMP (db-cAMP) or 8Br-cAMP or by the specific competitive inhibitor of protein kinase A, Rp-adenosine-3',5'-cyclic monophosphothioate triethylamine salt (Rp-cAMP). Expression of the PACAP receptor (PAC1) in neural stem cells was detected by both RT-PCR and immunoblot using an affinity-purified antibody. The PACAP selective antagonist, PACAP(6-38), had an inhibitory effect on the PACAP-induced differentiation of neural stem cells into astrocytes. These results indicate that PACAP acts on the PAC1 receptor on the plasma membrane of mouse neural stem cells, with the signal then transmitted intracellularly via a PAC1-coupled G protein, does not involve Gs. This signaling mechanism may thus play a crucial role in the differentiation of neural stem cells into astrocytes. 相似文献
56.
Mechanism for generation of hydrogen peroxide and change of mitochondrial membrane potential during rotenone-induced apoptosis 总被引:13,自引:0,他引:13
Rotenone, an inhibitor of NADH dehydrogenase complex, is a naturally occurring insecticide, which is capable of inducing apoptosis. Rotenone-induced apoptosis is considered to contribute to its anticancer effect and the etiology of Parkinson's disease (PD). We demonstrated that rotenone induced internucleosomal DNA fragmentation, DNA ladder formation, in human cultured cells, HL-60 (promyelocytic leukemia) and BJAB cells (B-cell lymphoma). Flow cytometry showed that rotenone induced H2O2 generation, followed by significant changes in the mitochondrial membrane potential (DeltaPsim). Caspase-3 activity increased in HL-60 cells in a time-dependent manner. These apoptotic events were delayed in HP100 cells, an H2O2-resistant clone of HL-60, confirming the involvement of H2O2 in apoptosis. Expression of anti-apoptotic protein, Bcl-2, in BJAB cells drastically inhibited DeltaPsim change and DNA ladder formation but not H2O2 generation, confirming the participation of mitochondrial dysfunction in apoptosis. NAD(P)H oxidase inhibitors prevented H2O2 generation and DNA ladder formation. These results suggest that rotenone induces O2(-)-derived H2O2 generation through inhibition of NADH dehydrogenase complex and/or activation of NAD(P)H oxidase, and H2O2 generation causes the disruption of mitochondrial membrane in rotenone-induced apoptosis. 相似文献
57.
58.
59.
A metalloprotease-disintegrin, MDC9/meltrin-gamma/ADAM9 and PKCdelta are involved in TPA-induced ectodomain shedding of membrane-anchored heparin-binding EGF-like growth factor. 总被引:8,自引:0,他引:8 下载免费PDF全文
Y Izumi M Hirata H Hasuwa R Iwamoto T Umata K Miyado Y Tamai T Kurisaki A Sehara-Fujisawa S Ohno E Mekada 《The EMBO journal》1998,17(24):7260-7272
The ectodomains of many proteins located at the cell surface are shed upon cell stimulation. One such protein is the heparin-binding EGF-like growth factor (HB-EGF) that exists in a membrane-anchored form which is converted to a soluble form upon cell stimulation with TPA, an activator of protein kinase C (PKC). We show that PKCdelta binds in vivo and in vitro to the cytoplasmic domain of MDC9/meltrin-gamma/ADAM9, a member of the metalloprotease-disintegrin family. Furthermore, the presence of constitutively active PKCdelta or MDC9 results in the shedding of the ectodomain of proHB-EGF, whereas MDC9 mutants lacking the metalloprotease domain, as well as kinase-negative PKCdelta, suppress the TPA-induced shedding of the ectodomain. These results suggest that MDC9 and PKCdelta are involved in the stimulus-coupled shedding of the proHB-EGF ectodomain. 相似文献
60.