全文获取类型
收费全文 | 2512篇 |
免费 | 130篇 |
国内免费 | 1篇 |
专业分类
2643篇 |
出版年
2022年 | 15篇 |
2021年 | 23篇 |
2020年 | 15篇 |
2019年 | 24篇 |
2018年 | 30篇 |
2017年 | 29篇 |
2016年 | 49篇 |
2015年 | 88篇 |
2014年 | 104篇 |
2013年 | 183篇 |
2012年 | 162篇 |
2011年 | 150篇 |
2010年 | 100篇 |
2009年 | 116篇 |
2008年 | 157篇 |
2007年 | 163篇 |
2006年 | 169篇 |
2005年 | 165篇 |
2004年 | 153篇 |
2003年 | 166篇 |
2002年 | 192篇 |
2001年 | 27篇 |
2000年 | 21篇 |
1999年 | 18篇 |
1998年 | 35篇 |
1997年 | 25篇 |
1996年 | 23篇 |
1995年 | 18篇 |
1994年 | 20篇 |
1993年 | 26篇 |
1992年 | 28篇 |
1991年 | 15篇 |
1990年 | 13篇 |
1989年 | 12篇 |
1988年 | 10篇 |
1987年 | 5篇 |
1986年 | 12篇 |
1985年 | 7篇 |
1984年 | 7篇 |
1983年 | 10篇 |
1982年 | 21篇 |
1981年 | 10篇 |
1980年 | 9篇 |
1979年 | 2篇 |
1978年 | 3篇 |
1977年 | 3篇 |
1976年 | 4篇 |
1972年 | 2篇 |
1969年 | 1篇 |
1968年 | 2篇 |
排序方式: 共有2643条查询结果,搜索用时 0 毫秒
81.
Neural recognition molecule NB-2/contactin 5 is expressed transiently during the first postnatal week in glutamatergic neurons of the central auditory system. Here, we investigated the effect of NB-2 deficiency on the auditory brainstem in mouse. While almost all principal neurons are wrapped with the calyces of Held in the medial nucleus of the trapezoid body (MNTB) in wild type, 8% of principal neurons in NB-2 knockout (KO) mice lack the calyces of Held at postnatal day (P) 6. At P10 and P15, apoptotic principal neurons were detected in NB-2 KO mice, but not in wild type. Apoptotic cells were also increased in the ventral cochlear nucleus (VCN) of NB-2 KO mice, which contains bushy neurons projecting to the MNTB and the lateral superior olive (LSO). At the age of 1 month, the number of principal neurons in the MNTB and of glutamatergic synapses in the LSO was reduced in NB-2 KO mice. Finally, interpeak latencies for auditory brainstem response waves II-III and III-IV were significantly increased in NB-2 KO mice. Together, these findings suggest that NB-2 deficiency causes a deficit in synapse formation and then induces apoptosis in MNTB and VCN neurons, affecting auditory brainstem function. 相似文献
82.
Ikeda H Watanabe N Ishii I Shimosawa T Kume Y Tomiya T Inoue Y Nishikawa T Ohtomo N Tanoue Y Iitsuka S Fujita R Omata M Chun J Yatomi Y 《Journal of lipid research》2009,50(3):556-564
Sphingosine 1-phosphate (S1P), a bioactive lipid mediator, stimulates proliferation and contractility in hepatic stellate cells, the principal matrix-producing cells in the liver, and inhibits proliferation via S1P receptor 2 (S1P(2)) in hepatocytes in rats in vitro. A potential role of S1P and S1P(2) in liver regeneration and fibrosis was examined in S1P(2)-deficient mice. Nuclear 5-bromo-2'-deoxy-uridine labeling, proliferating cell nuclear antigen (PCNA) staining in hepatocytes, and the ratio of liver weight to body weight were enhanced at 48 h in S1P(2)-deficient mice after a single carbon tetrachloride (CCl(4)) injection. After dimethylnitrosamine (DMN) administration with a lethal dose, PCNA staining in hepatocytes was enhanced at 48 h and survival rate was higher in S1P(2)-deficient mice. Serum aminotransferase level was unaltered in those mice compared with wild-type mice in both CCl(4)- and DMN-induced liver injury, suggesting that S1P(2) inactivation accelerated regeneration not as a response to enhanced liver damage. After chronic CCl(4) administration, fibrosis was less apparent, with reduced expression of smooth-muscle alpha-actin-positive cells in the livers of S1P(2)-deficient mice, suggesting that S1P(2) inactivation ameliorated CCl(4)-induced fibrosis due to the decreased accumulation of hepatic stellate cells. Thus, S1P plays a significant role in regeneration and fibrosis after liver injury via S1P(2). 相似文献
83.
Tsubasa Fukue Motohide Tamura Ryo Kandori Nobuhiko Kusakabe James H. Hough Jeremy Bailey Douglas C. B. Whittet Philip W. Lucas Yasushi Nakajima Jun Hashimoto 《Origins of life and evolution of the biosphere》2010,40(3):335-346
We present a wide-field (∼6′ × 6′) and deep near-infrared (K
s
band: 2.14 μm) circular polarization image in the Orion nebula, where massive stars and many low-mass stars are forming.
Our results reveal that a high circular polarization region is spatially extended (∼0.4 pc) around the massive star-forming
region, the BN/KL nebula. However, other regions, including the linearly polarized Orion bar, show no significant circular
polarization. Most of the low-mass young stars do not show detectable extended structure in either linear or circular polarization,
in contrast to the BN/KL nebula. If our solar system formed in a massive star-forming region and was irradiated by net circularly
polarized radiation, then enantiomeric excesses could have been induced, through asymmetric photochemistry, in the parent
bodies of the meteorites and subsequently delivered to Earth. These could then have played a role in the development of biological
homochirality on Earth. 相似文献
84.
Murakami G Tsurugizawa T Hatanaka Y Komatsuzaki Y Tanabe N Mukai H Hojo Y Kominami S Yamazaki T Kimoto T Kawato S 《Biochemical and biophysical research communications》2006,351(2):553-558
Modulation of hippocampal synaptic plasticity by estrogen has been attracting much attention. Here, we demonstrated the rapid effect of 17beta-estradiol on the density and morphology of spines in the stratum oriens (s.o., basal side) and in the stratum lacunosum-moleculare (s.l.m., apical side) by imaging Lucifer Yellow-injected CA1 neurons in adult male rat hippocampal slices, because spines in s.o. and s.l.m. have been poorly understood as compared with spines in the stratum radiatum. The application of 1nM estradiol-induced a rapid increase in the density of spines of pyramidal neurons within 2h. This increase by estradiol was blocked by Erk MAP kinase inhibitor and estrogen receptor inhibitor in both regions. Effect of blockade by agonists of AMPA receptors and NMDA receptors was different between s.o. and s.l.m. In both regions, ERalpha agonist PPT induced the same enhancing effect of spinogenesis as that induced by estradiol. 相似文献
85.
Tsuyoshi S. Nakamura Yasuyuki Suda Kenji Muneshige Yuji Fujieda Yuuya Okumura Ichiro Inoue Takayuki Tanaka Tetsuo Takahashi Hideki Nakanishi Xiao-Dong Gao Yasushi Okada Aaron M. Neiman Hiroyuki Tachikawa 《PLoS genetics》2021,17(8)
Vps13 family proteins are proposed to function in bulk lipid transfer between membranes, but little is known about their regulation. During sporulation of Saccharomyces cerevisiae, Vps13 localizes to the prospore membrane (PSM) via the Spo71–Spo73 adaptor complex. We previously reported that loss of any of these proteins causes PSM extension and subsequent sporulation defects, yet their precise function remains unclear. Here, we performed a genetic screen and identified genes coding for a fragment of phosphatidylinositol (PI) 4-kinase catalytic subunit and PI 4-kinase noncatalytic subunit as multicopy suppressors of spo73Δ. Further genetic and cytological analyses revealed that lowering PI4P levels in the PSM rescues the spo73Δ defects. Furthermore, overexpression of VPS13 and lowering PI4P levels synergistically rescued the defect of a spo71Δ spo73Δ double mutant, suggesting that PI4P might regulate Vps13 function. In addition, we show that an N-terminal fragment of Vps13 has affinity for the endoplasmic reticulum (ER), and ER-plasma membrane (PM) tethers localize along the PSM in a manner dependent on Vps13 and the adaptor complex. These observations suggest that Vps13 and the adaptor complex recruit ER-PM tethers to ER-PSM contact sites. Our analysis revealed that involvement of a phosphoinositide, PI4P, in regulation of Vps13, and also suggest that distinct contact site proteins function cooperatively to promote de novo membrane formation. 相似文献
86.
Makoto Nakamura Yasushi Makino Chika Takagi Tohru Yamagaki Masaaki Sato 《Glycoconjugate journal》2017,34(4):563-574
Glycogen phosphorylase (GP) is an allosteric enzyme whose catalytic site comprises six subsites (SG1, SG?1, SG?2, SG?3, SG?4, and SP) that are complementary to tandem five glucose residues and one inorganic phosphate molecule, respectively. In the catalysis of GP, the nonreducing-end glucose (Glc) of the maltooligosaccharide substrate binds to SG1 and is then phosphorolyzed to yield glucose 1-phosphate. In this study, we probed the catalytic site of rabbit muscle GP using pyridylaminated-maltohexaose (Glcα1–4Glcα1–4Glcα1–4Glcα1–4Glcα1–4GlcPA, where GlcPA = 1-deoxy-1-[(2-pyridyl)amino]-D-glucitol]; abbreviated as PA-0) and a series of specifically modified PA-0 derivatives (Glc m -AltNAc-Glc n -GlcPA, where m + n = 4 and AltNAc is 3-acetoamido-3-deoxy-D-altrose). PA-0 served as an efficient substrate for GP, whereas the other PA-0 derivatives were not as good as the PA-0, indicating that substrate recognition by all the SG1 –SG?4 subsites was important for the catalysis of GP. By comparing the initial reaction rate toward the PA-0 derivatives (V derivative) with that toward PA-0 (V PA-0), we found that the value of V derivative/V PA-0 decreased significantly as the level of allosteric activation of GP increased. These results suggest that some conformational changes have taken place in the maltooligosaccharide-binding region of the GP catalytic site during allosteric regulation. 相似文献
87.
88.
Human T-cell leukemia virus type 1 HBZ protein bypasses the targeting function of ubiquitination 总被引:1,自引:0,他引:1
Isono O Ohshima T Saeki Y Matsumoto J Hijikata M Tanaka K Shimotohno K 《The Journal of biological chemistry》2008,283(49):34273-34282
Human T-cell leukemia virus type 1 (HTLV-1) encodes an antisense viral gene product termed HTLV-1 basic leucine-zipper factor (HBZ). HBZ forms heterodimers with c-Jun, a member of the AP-1 family, and promotes its proteasomal degradation. Although most proteasomal substrates are targeted for degradation via conjugation of polyubiquitin chains, we show that ubiquitination is not required for HBZ-mediated proteasomal degradation of c-Jun. We demonstrate that HBZ directly interacts with both the 26 S proteasome and c-Jun and facilitates the delivery of c-Jun to the proteasome without ubiquitination. HBZ acts as a tethering factor between the 26 S proteasome and its substrate, thereby bypassing the targeting function of ubiquitination. These findings disclose a novel viral strategy to utilize the cellular proteolytic system for viral propagation. 相似文献
89.
Nakahara Y Watanabe M Fujita A Kanamori Y Tanaka D Iwata K Furuki T Sakurai M Kikawada T Okuda T 《Journal of insect physiology》2008,54(8):1220-1225
Strategies to combat desiccation are critical for organisms living in arid and semi-arid areas. Larvae of the Australian chironomid Paraborniella tonnoiri resist desiccation by reducing water loss. In contrast, larvae of the African species Polypedilum vanderplanki can withstand almost complete dehydration, referred to as anhydrobiosis. For successful anhydrobiosis, the dehydration rate of P. vanderplanki larvae has to be controlled. Here, we desiccated larvae by exposing them to different drying regimes, each progressing from high to low relative humidity, and examined survival after rehydration. In larvae of P. vanderplanki, reactions following desiccation can be categorized as follows: (I) no recovery at all (direct death), (II) dying by unrepairable damages after rehydration (delayed death), and (III) full recovery (successful anhydrobiosis). Initial conditions of desiccation severely affected survival following rehydration, i.e. P. vanderplanki preferred 100% relative humidity where body water content decreased slightly. In subsequent conditions, unfavorable dehydration rate, such as more than 0.7 mg water lost per day, resulted in markedly decreased survival rate of rehydrated larvae. Slow dehydration may be required for the synthesis and distribution of essential molecules for anhydrobiosis. Larvae desiccated at or above maximum tolerable rates sometimes showed temporary recovery but died soon after. 相似文献
90.
Nakazawa H Okada K Kobayashi R Kubota T Onodera T Ochiai N Omata N Ogasawara W Okada H Morikawa Y 《Applied microbiology and biotechnology》2008,81(4):681-689
The genes encoding the catalytic domains (CD) of the three endoglucanases (EG I; Cel7B, EG II; Cel5A, and EG III; Cel12A)
from Trichoderma reesei QM9414 were expressed in Escherichia coli strains Rosetta-gami B (DE3) pLacI or Origami B (DE3) pLacI and were found to produce functional intracellular proteins.
Protein production by the three endoglucanase transformants was evaluated as a function of growth temperature. Maximal productivity
of EG I-CD at 15°C, EG II-CD at 20°C and EG III at 37°C resulted in yields of 6.9, 72, and 50 mg/l, respectively. The endoglucanases
were purified using a simple purification method based on removing E. coli proteins by isoelectric point precipitation. Specific activity toward carboxymethyl cellulose was found to be 65, 49, and
15 U/mg for EG I-CD, EG II-CD, and EG III, respectively. EG II-CD was able to cleave 1,3–1,4-β-d-glucan and soluble cellulose derivatives. EG III was found to be active against cellulose, 1,3–1,4-β-d-glucan and xyloglucan, while EG I-CD was active against cellulose, 1,3–1,4-β-d-glucan, xyloglucan, xylan, and mannan. 相似文献