全文获取类型
收费全文 | 504篇 |
免费 | 21篇 |
国内免费 | 2篇 |
专业分类
527篇 |
出版年
2024年 | 2篇 |
2023年 | 8篇 |
2022年 | 13篇 |
2021年 | 26篇 |
2020年 | 14篇 |
2019年 | 11篇 |
2018年 | 17篇 |
2017年 | 11篇 |
2016年 | 8篇 |
2015年 | 13篇 |
2014年 | 23篇 |
2013年 | 31篇 |
2012年 | 22篇 |
2011年 | 39篇 |
2010年 | 21篇 |
2009年 | 13篇 |
2008年 | 23篇 |
2007年 | 21篇 |
2006年 | 24篇 |
2005年 | 21篇 |
2004年 | 11篇 |
2003年 | 12篇 |
2002年 | 9篇 |
2001年 | 7篇 |
2000年 | 8篇 |
1999年 | 6篇 |
1998年 | 3篇 |
1997年 | 3篇 |
1994年 | 6篇 |
1993年 | 6篇 |
1992年 | 8篇 |
1991年 | 9篇 |
1990年 | 12篇 |
1989年 | 4篇 |
1988年 | 3篇 |
1987年 | 3篇 |
1986年 | 9篇 |
1985年 | 4篇 |
1984年 | 3篇 |
1983年 | 4篇 |
1982年 | 2篇 |
1981年 | 2篇 |
1979年 | 3篇 |
1977年 | 3篇 |
1973年 | 6篇 |
1970年 | 2篇 |
1969年 | 9篇 |
1967年 | 2篇 |
1966年 | 1篇 |
1965年 | 1篇 |
排序方式: 共有527条查询结果,搜索用时 15 毫秒
1.
N. Ghanem J. M. Lobaccaro C. Buresi M. Abbal G. Halaby C. Sultan G. Lefranc 《Human genetics》1990,86(2):117-125
Summary Defects in the enzyme, steroid 21-hydroxylase, result in congenital adrenal hyperplasia (CAH), a common autosomal recessive disorder of cortisol biosynthesis. The gene encoding this protein (CYP21B) and a closely linked pseudogene (CYP21A) have been mapped in the HLA complex on chromosome 6p, adjacent to the complement genes C4B and C4A, about 80 kb from the factor B gene. Molecular analyses of patients with CAH have shown that the cause of the defect may be either a deletion, a point mutation or a conversion of the active gene. Linkage of the disease to HLA has previously been studied by several groups. We have analyzed DNAs from patients with classical and non-classical CAH and from their family members, by probing with CYP21, C4 and BF cDNAs. In 70% of the CAH haplotypes studied, the defective CYP21B gene was indistinguishable from its structurally intact corresponding gene in Southern blot analysis, and presumably bore point mutations. In the remaining chromosomes, evidence for gene conversions, deletions and various deleterious mutations of the CYP21B gene is given. Moreover, our linkage studies show that a polymorphic TaqI cleavage site in the factor B gene, recently described by us, may be a new and useful genetic marker, because we found this TaqI restriction site only in unaffected haplotypes carrying functional CYP21B genes and, therefore, in negative association with the defective CYP21B gene. 相似文献
2.
C Sultan A Bonardet B Bonnal B Descomps J C De Kerleau H Bonnet R Jean A C De Paulet 《Comptes rendus des séances de la Société de biologie et de ses filiales》1977,171(1):131-135
Plasma prolactin levels were determined by an homologous radio-immuno assay in normal children: in cord blood, at the first day of life, during childhood and along puberty. 1. In both sexes, there is a very important secretion of prolactin during the neonatal period. 2. Longitudinal studies make obvious a different pattern of plasma prolactin in boys and in girls at puberty. 相似文献
3.
A. M. N. Sultan 《Molecular and cellular biochemistry》1992,113(1):17-23
This work investigates the effect of alloxan-induced short-term diabetes (24 h) on D-3-hydroxybutyrate metabolism at physiological
and non-physiological concentrations of the ketone body in the isolated non-working perfused rat heart. Also the effect of
insulin (2 mU.ml−1) on D-3-hydroxybutyrate metabolism was investigated in hearts from normal and diabetic rats. The rates of D-3-hydroxybutyrate
utilization and oxidation and of acetoacetate production were proportional to D-3-hydroxybutyrate concentration. The utilization
of D-3-hydroxybutyrate showed saturation kinetics in hearts from normal and diabetic rats, in the presence and absence of
insulin. Acute short-term diabetes augmented D-3-hydroxybutyrate utilization and oxidation at 1.25 and 2.5 mM DL-3-HB, with
no significant effect at higher concentrations, but increased acetoacetate production at all investigated concentrations.
In hearts from normal rats, insulin enhanced D-3-hydroxybutyrate utilization and oxidation at 2.5, 5, and 10 mM DL-3-HB, but
no effect was observed at the lowest (1.25 mM) and highest (16 mM) DL-3-HB concentrations. Insulin had no effect on D-3-hydroxybutyrate
metabolism in hearts from diabetic rats. No significant effect of insulin on the rate of acetoacetate production in normal
and diabetic states was observed. 相似文献
4.
5.
6.
Samir Attoub Kholoud Arafat An Gélaude Mahmood Ahmed Al Sultan Marc Bracke Peter Collin Takashi Takahashi Thomas E. Adrian Olivier De Wever 《PloS one》2013,8(1)
A major challenge for oncologists and pharmacologists is to develop less toxic drugs that will improve the survival of lung cancer patients. Frondoside A is a triterpenoid glycoside isolated from the sea cucumber, Cucumaria frondosa and was shown to be a highly safe compound. We investigated the impact of Frondoside A on survival, migration and invasion in vitro, and on tumor growth, metastasis and angiogenesis in vivo alone and in combination with cisplatin. Frondoside A caused concentration-dependent reduction in viability of LNM35, A549, NCI-H460-Luc2, MDA-MB-435, MCF-7, and HepG2 over 24 hours through a caspase 3/7-dependent cell death pathway. The IC50 concentrations (producing half-maximal inhibition) at 24 h were between 1.7 and 2.5 µM of Frondoside A. In addition, Frondoside A induced a time- and concentration-dependent inhibition of cell migration, invasion and angiogenesis in vitro. Frondoside A (0.01 and 1 mg/kg/day i.p. for 25 days) significantly decreased the growth, the angiogenesis and lymph node metastasis of LNM35 tumor xenografts in athymic mice, without obvious toxic side-effects. Frondoside A (0.1–0.5 µM) also significantly prevented basal and bFGF induced angiogenesis in the CAM angiogenesis assay. Moreover, Frondoside A enhanced the inhibition of lung tumor growth induced by the chemotherapeutic agent cisplatin. These findings identify Frondoside A as a promising novel therapeutic agent for lung cancer. 相似文献
7.
Anil-Inevi Muge Sağlam-Metiner Pelin Kabak Evrim Ceren Gulce-Iz Sultan 《Molecular biology reports》2020,47(1):97-109
Molecular Biology Reports - Breast cancer is one of the most common cancer types among women in which early tumor invasion leads to metastases and death. EpCAM (epithelial cellular adhesion... 相似文献
8.
Margret Rave-Fränk Ihtzaz Ahmed Malik Hans Christiansen Naila Naz Sadaf Sultan Ahmad Amanzada Martina Blaschke Silke Cameron Shakil Ahmad Clemens Friedrich Hess Giuliano Ramadori Federico Moriconi 《Radiation and environmental biophysics》2013,52(3):321-338
The liver is considered a radiosensitive organ. However, in rats, high single-dose irradiation (HDI) showed only mild effects. Consequences of fractionated irradiation (FI) in such an animal model have not been studied so far. Rats were exposed to selective liver FI (total dose 60 Gy, 2 Gy/day) or HDI (25 Gy) and were killed three months after the end of irradiation. To study acute effects, HDI-treated rats were additionally killed at several time points between 1 and 48 h. Three months after irradiation, no differences between FI and HDI treatment were found for macroscopically detectable small “scars” on the liver surface and for an increased number of neutrophil granulocytes distributed in the portal fields and through the liver parenchyma. As well, no changes in HE-stained tissues or clear signs of fibrosis were found around the portal vessels. Differences were seen for the number of bile ducts being increased in FI- but not in HDI-treated livers. Serum levels indicative of liver damage were determined for alkaline phosphatase (AP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyltransferase (γGT) and lactate dehydrogenase (LDH). A significant increase of AP was detected only after FI while HDI led to the significant increases of AST and LDH serum levels. By performing RT-PCR, we detected up-regulation of matrix metalloproteinases, MMP-2, MMP-9, MMP-14, and of their inhibitors, TIMP-1, TIMP-2 and TIMP-3, shortly after HDI, but not at 3 month after FI or HDI. Overall, we saw punctual differences after FI and HDI, and a diffuse formation of small scars at the liver surface. Lack of “provisional clot”-formation and absence of recruitment of mononuclear phagocytes could be one explanation for scar formation as incomplete repair response to irradiation. 相似文献
9.
ABSTRACTChemotherapy administration may result in the disruption of circadian rhythms and impairment of quality of life (QoL) of cancer patients. Nevertheless, we have little knowledge on the long-term consequences of chemotherapy and the effects of hospitalization. In the present study, we employed the two-factor repeated-measure cross-sectional design to determine the effects of chemotherapy and hospitalization on rest-activity (RA) rhythm and QoL of breast cancer patients. Initially, we randomly selected 39 inpatients and 42 outpatients, scheduled to receive six cycles of chemotherapy, from the Regional Cancer Center (RCC), Raipur, India. Finally, 30 patients in each group were included in the current study. We monitored circadian RA rhythm and QoL using wrist actigraphy and QLQ-C30 and QLQ-BR23, respectively, during the 1st (C1), 3rd (C3) and 6th (C6) chemotherapy cycles. Results revealed that with the progression of chemotherapy cycles (from C1 to C6), all rhythm parameters, namely mesor, amplitude, acrophase, rhythm quotient (RQ), circadian quotient (CQ), peak activity (PA), dichotomy index and autocorrelation coefficient, significantly decreased in both cancer in- and outpatients. In both groups of patients and during C1–C6, all functional and global QoL measures of QLQ-C30 and QLQ-BR23 significantly decreased and the symptoms significantly increased, except constipation, body image, sexual functioning and future perspectives in outpatients. The hospitalization exacerbated the problems associated with the RA rhythm and the QoL of the patients. In conclusion, the current study highlighted the negative consequences of hospitalization among inpatients, irrespective of the stage of cancer. We, therefore, recommend that cancer patients should be administered with chemotherapy as outpatients. The proposed protocol might have a covert bearing on the expression of better physiological state leading to satisfactory treatment outcomes. 相似文献
10.
Antoine G. Almonte Laura H. Qadri Faraz A. Sultan Jennifer A. Watson Daniel J. Mount Gavin Rumbaugh J. David Sweatt 《Journal of neurochemistry》2013,124(1):109-122
Protease‐activated receptor‐1 (PAR1) is an unusual G‐protein coupled receptor (GPCR) that is activated through proteolytic cleavage by extracellular serine proteases. Although previous work has shown that inhibiting PAR1 activation is neuroprotective in models of ischemia, traumatic injury, and neurotoxicity, surprisingly little is known about PAR1's contribution to normal brain function. Here, we used PAR1?/? mice to investigate the contribution of PAR1 function to memory formation and synaptic function. We demonstrate that PAR1?/? mice have deficits in hippocampus‐dependent memory. We also show that while PAR1?/? mice have normal baseline synaptic transmission at Schaffer collateral‐CA1 synapses, they exhibit severe deficits in N‐methyl‐d ‐aspartate receptor (NMDAR)‐dependent long‐term potentiation (LTP). Mounting evidence indicates that activation of PAR1 leads to potentiation of NMDAR‐mediated responses in CA1 pyramidal cells. Taken together, this evidence and our data suggest an important role for PAR1 function in NMDAR‐dependent processes subserving memory formation and synaptic plasticity. 相似文献