首页 | 本学科首页   官方微博 | 高级检索  
文章检索
  按 检索   检索词:      
出版年份:   被引次数:   他引次数: 提示:输入*表示无穷大
  收费全文   574篇
  免费   27篇
  国内免费   1篇
  602篇
  2024年   2篇
  2022年   12篇
  2021年   16篇
  2020年   4篇
  2019年   12篇
  2018年   12篇
  2017年   8篇
  2016年   21篇
  2015年   27篇
  2014年   36篇
  2013年   47篇
  2012年   42篇
  2011年   42篇
  2010年   27篇
  2009年   26篇
  2008年   44篇
  2007年   28篇
  2006年   33篇
  2005年   15篇
  2004年   29篇
  2003年   20篇
  2002年   17篇
  2001年   4篇
  1999年   4篇
  1998年   2篇
  1996年   2篇
  1995年   3篇
  1993年   2篇
  1991年   2篇
  1990年   4篇
  1988年   3篇
  1986年   4篇
  1985年   2篇
  1984年   6篇
  1982年   4篇
  1981年   5篇
  1980年   2篇
  1979年   2篇
  1977年   2篇
  1976年   5篇
  1970年   2篇
  1959年   1篇
  1958年   1篇
  1956年   1篇
  1955年   1篇
  1953年   2篇
  1952年   1篇
  1950年   1篇
  1945年   1篇
  1935年   1篇
排序方式: 共有602条查询结果,搜索用时 0 毫秒
591.
592.
The accessory glands of male Melanoplus sanguinipes contain an oviposition stimulant. Injection of gland extracts from mature males induces oviposition in 75 per cent of capable virgin females within 24 hr. Injection of gland extracts from allatectomized males produces no stimulatory effect. Gland extracts from mature males contain two antigens which cannot be detected in gland extracts from allatectomized males. However, both antigens can be detected in gland extracts from allatectomized males 3 days after treatment with juvenile hormone.Anion-exchange chromatography of mature gland extracts yielded two fractions which, when injected into virgin females, induced oviposition in 71 per cent of capable insects within 24 hr. These two fractions are immunologically identical to the two antigens which are absent from gland extracts of allatectomized males. We suggest that synthesis of the oviposition stimulant in Melanoplus is controlled by the corpus allatum.Injection of brain extract also induces oviposition in 100 per cent of capable virgin females within 24 hr. A possible rôle for the brain in the oviposition process is discussed.  相似文献   
593.
The SAR of a series of novel pyrido[3,4-d]pyramid-4-ylamine mGluR1 antagonists is described. The multiple of the unbound Ki in cerebrospinal fluid necessary to give morphine like analgesic effects in an electromyograph pinch model in rodents is determined and the effect of structure on CNS penetration examined.  相似文献   
594.

Background

Vitamin D deficiency is associated with smaller volume of optic chiasm in older adults, indicating a possible loss of the visual axons and their cellular bodies. Our objective was to determine whether vitamin D deficiency in older adults is associated with reduced thickness of the ganglion cell complex(GCC) and of the retinal nerve fibre layer(RNFL), as measured with high-definition optical coherence tomography(HD-OCT).

Methods

Eighty-five French older community-dwellers without open-angle glaucoma and patent age-related macular degeneration(mean, 71.1±4.7years; 45.9%female) from the GAIT study were separated into 2 groups according to serum 25OHD level(i.e., deficient≤25nmol/L or sufficient>25nmol/L). Measurements of GCC and RNFL thickness were performed using HD-OCT. Age, gender, body mass index, number of comorbidities, dementia, functional autonomy, intracranial volume, visual acuity, serum calcium concentration and season of testing were considered as potential confounders.

Results

Mean serum 25OHD concentration was 58.4±26.8nmol/L. Mean logMAR visual acuity was 0.03±0.06. Mean visual field mean deviation was -1.25±2.29dB. Patients with vitamin D deficiency(n=11) had a reduced mean GCC thickness compared to those without vitamin D deficiency(72.1±7.4μm versus 77.5±7.5μm, P=0.028). There was no difference of the mean RNFL thickness in these two groups(P=0.133). After adjustment for potential confounders, vitamin D deficiency was associated with reduced GCC thickness(ß=-5.12, P=0.048) but not RNFL thickness(ß=-9.98, P=0.061). Specifically, vitamin D deficiency correlated with the superior medial GCC area(P=0.017) and superior temporal GCC area(P=0.010).

Conclusions

Vitamin D deficiency in older patients is associated with reduced mean GCC thickness, which can represent an early stage of optic nerve damage, prior to RNFL loss.  相似文献   
595.
Chloride intracellular channel 2 (CLIC2), a newly discovered small protein distantly related to the glutathione transferase (GST) structural family, is highly expressed in cardiac and skeletal muscle, although its physiological function in these tissues has not been established. In the present study, [3H]ryanodine binding, Ca2+ efflux from skeletal sarcoplasmic reticulum (SR) vesicles, single channel recording, and cryo-electron microscopy were employed to investigate whether CLIC2 can interact with skeletal ryanodine receptor (RyR1) and modulate its channel activity. We found that: (1) CLIC2 facilitated [3H]ryanodine binding to skeletal SR and purified RyR1, by increasing the binding affinity of ryanodine for its receptor without significantly changing the apparent maximal binding capacity; (2) CLIC2 reduced the maximal Ca2+ efflux rate from skeletal SR vesicles; (3) CLIC2 decreased the open probability of RyR1 channel, through increasing the mean closed time of the channel; (4) CLIC2 bound to a region between domains 5 and 6 in the clamp-shaped region of RyR1; (5) and in the same clamp region, domains 9 and 10 became separated after CLIC2 binding, indicating CLIC2 induced a conformational change of RyR1. These data suggest that CLIC2 can interact with RyR1 and modulate its channel activity. We propose that CLIC2 functions as an intrinsic stabilizer of the closed state of RyR channels.  相似文献   
596.
597.
598.
599.
    
To engineer a host cell line that produces defucosylated mAbs with superior antibody‐dependent cellular cytotoxicity, we disrupted α‐1, 6 fucosyltransferase (FUT8 ) gene in CHO‐S (CHO is Chinese hamster ovary) cells by clustered regularly interspaced short palindromic repeats‐CRISPR associated nuclease 9. The gene knockout cell line was evaluated for growth, stability, and product quality. The growth profile of FUT8 gene knockout CHO‐S (FUT8 ?/?) cells was comparable with wild type CHO‐S cells. FUT8 catalyzes the transfer of a fucose residue from GDP‐fucose to N‐glycans residue. Defucosylated IgG1 antibodies produced by FUT8 ?/? cells showed increased binding affinities to human FcγRIIIa and higher activities in mediating antibody‐dependent cellular cytotoxicity, comparing with conventional fucosylated IgG1. Our results demonstrated the potential of using the clustered regularly interspaced short palindromic repeats‐CRISPR associated nuclease 9 technology in cell line engineering for biopharmaceutical industrial applications.  相似文献   
600.
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号