全文获取类型
收费全文 | 2309篇 |
免费 | 112篇 |
专业分类
2421篇 |
出版年
2022年 | 10篇 |
2021年 | 9篇 |
2020年 | 6篇 |
2019年 | 16篇 |
2018年 | 31篇 |
2017年 | 22篇 |
2016年 | 41篇 |
2015年 | 64篇 |
2014年 | 89篇 |
2013年 | 149篇 |
2012年 | 177篇 |
2011年 | 151篇 |
2010年 | 111篇 |
2009年 | 85篇 |
2008年 | 152篇 |
2007年 | 145篇 |
2006年 | 148篇 |
2005年 | 156篇 |
2004年 | 135篇 |
2003年 | 138篇 |
2002年 | 142篇 |
2001年 | 15篇 |
2000年 | 12篇 |
1999年 | 21篇 |
1998年 | 36篇 |
1997年 | 48篇 |
1996年 | 22篇 |
1995年 | 25篇 |
1994年 | 10篇 |
1993年 | 20篇 |
1992年 | 12篇 |
1991年 | 21篇 |
1990年 | 14篇 |
1989年 | 14篇 |
1988年 | 4篇 |
1987年 | 6篇 |
1986年 | 11篇 |
1985年 | 14篇 |
1984年 | 15篇 |
1983年 | 8篇 |
1982年 | 20篇 |
1981年 | 20篇 |
1980年 | 16篇 |
1979年 | 13篇 |
1978年 | 10篇 |
1977年 | 5篇 |
1976年 | 10篇 |
1975年 | 5篇 |
1973年 | 5篇 |
1971年 | 4篇 |
排序方式: 共有2421条查询结果,搜索用时 15 毫秒
31.
32.
Yuling Chi Jean-Francois Jasmin Yoshinori Seki Michael P. Lisanti Maureen J. Charron David J. Lefer Victor L. Schuster 《PloS one》2015,10(6)
Inhibiting the synthesis of endogenous prostaglandins with nonsteroidal anti-inflammatory drugs exacerbates arterial hypertension. We hypothesized that the converse, i.e., raising the level of endogenous prostaglandins, might have anti-hypertensive effects. To accomplish this, we focused on inhibiting the prostaglandin transporter PGT (SLCO2A1), which is the obligatory first step in the inactivation of several common PGs. We first examined the role of PGT in controlling arterial blood pressure blood pressure using anesthetized rats. The high-affinity PGT inhibitor T26A sensitized the ability of exogenous PGE2 to lower blood pressure, confirming both inhibition of PGT by T26A and the vasodepressor action of PGE2 T26A administered alone to anesthetized rats dose-dependently lowered blood pressure, and did so to a greater degree in spontaneously hypertensive rats than in Wistar-Kyoto control rats. In mice, T26A added chronically to the drinking water increased the urinary excretion and plasma concentration of PGE2 over several days, confirming that T26A is orally active in antagonizing PGT. T26A given orally to hypertensive mice normalized blood pressure. T26A increased urinary sodium excretion in mice and, when added to the medium bathing isolated mouse aortas, T26A increased the net release of PGE2 induced by arachidonic acid, inhibited serotonin-induced vasoconstriction, and potentiated vasodilation induced by exogenous PGE2. We conclude that pharmacologically inhibiting PGT-mediated prostaglandin metabolism lowers blood pressure, probably by prostaglandin-induced natriuresis and vasodilation. PGT is a novel therapeutic target for treating hypertension. 相似文献
33.
Eiji Ichishima Yoshinori Tsuruda Taro Ushijima Takehiko Nomi Shoji Suzuki Michio Takeuchi Akiko Yamane 《Current microbiology》1980,4(2):85-89
The enzymological, physical, and immunological properties of soluble and bound forms of intracellular acid carboxypeptidase
isolated from fresh mycelia ofAspergillus saitoi are reported. In the broken mycelia, about 60% of the total activity was found in the 2,000×g precipitate, with most of the remainder in the 100,000×g supernantant. The highly purified enzymes, Ia and Ib, from the 100,000×g supernatant were found to be homogeneous by such criteria as disc gel electrophoresis at pH 9.4 The bound enzyme, II, was
solubilized from the 2,000×g precipitate by self-digestion at pH 6.4 and was highly purified by chromotography. The two forms of intracellular enzymes,
the soluble enzymes (Ia and Ib) from the 100,00×g supernatant and the solubilized enzyme (II) from the 2,000×g precipitate, were closely related to, but not completely identical with, the extracellular acid carboxypeptidase. 相似文献
34.
Elevated IL-7 in the target tissues is closely associated with multiple autoimmune disorders, including Sjögren’s syndrome (SS). We recently found that IL-7 plays an essential role in the development and onset of primary SS (pSS) in C57BL/6.NOD-Aec1Aec2 mice, a well-defined mouse model of primary SS. However, environmental signals that cause excessive IL-7 production are not well-characterized. Innate immune signaling plays a critical role in shaping the adaptive immune responses including autoimmune responses. We and others have previously shown that innate immune signaling can induce IL-7 expression in lungs and intestines of C57BL/6 mice. In this study, we characterized the effects of poly I:C, a double-stranded RNA analog and toll-like receptor 3 agonist, on the induction of IL-7 expression in salivary glands and on pSS development. We showed that poly I:C administration to C57BL/6 mice rapidly induced IL-7 expression in the salivary glands in a type 1 IFN- and IFN-γ-dependent manner. Moreover, poly I:C-induced IL-7 contributed to the optimal up-regulation of CXCL9 in the salivary glands, which may subsequently promote recruitment of more IFN-γ-producing T cells. Repeated administration of poly I:C to C57BL/6.NOD-Aec1Aec2 mice accelerated the development of SS-like exocrinopathy, and this effect was abolished by the blockade of IL-7 receptor signaling with a neutralizing antibody. Finally, poly I:C or a combination of IFN-α and IFN-γ induced IL-7 gene expression and protein production in a human salivary gland epithelial cell line. Hence, we demonstrate that IL-7 expression in the salivary gland cells can be induced by poly I:C and delineate a crucial mechanism by which innate immune signals facilitate the development of pSS, which is through induction of IL-7 in the target tissues. 相似文献
35.
Masaki Honda Tatsuya Kudo Takahiro Kuwa Takuma Higashiura Tetsuya Fukaya Yoshinori Inoue 《Bioscience, biotechnology, and biochemistry》2017,81(2):365-371
Lycopene has a large number of geometric isomers caused by E/Z isomerization at arbitrary sites within the 11 conjugated double bonds, offering varying characteristics related to features such as antioxidant capacity and bioavailability. However, the geometric structures of only a few lycopene Z-isomers have been thoroughly identified from natural sources. In this study, seven multi-Z-isomers of lycopene, (9Z,13′Z)-, (5Z,13Z,9′Z)-, (9Z,9′Z)-, (5Z,13′Z)-, (5Z,9′Z)-, (5Z,9Z,5′Z)-, and (5Z,9Z)-lycopene, were obtained from tomato samples by thermal isomerization, and then isolated by elaborate chromatography, and fully assigned using proton nuclear magnetic resonance. Moreover, the theoretically preferred pathway from (all-E)-lycopene to di-Z-isomers was examined with a computational approach using a Gaussian program. Fine-tuning of the HPLC separation conditions led to the discovery of novel multi-Z-isomers, and whose formation was supported by advanced theoretical calculations. 相似文献
36.
Yoshinori Sato Hayato Horiuchi Shinji Fukasawa Shingo Takesawa Jun Hirayama 《Biochemistry and Biophysics Reports》2021
In hemodialysis (HD), the patient's blood is purified via circulation in an extracorporeal circuit containing a dialyzer. In the manufacturing process of polysulfone (PSu) membrane dialyzers, the membranes are hydrophilized via the addition of the hydrophilic agent polyvinylpyrrolidone (PVP) to increase their hydraulic permeability. The elution of PVP from the membrane reduces the membrane's hydraulic permeability, and the eluted PVP could cause adverse effects in the human body. Therefore, it is important to identify the factors that induce PVP elution from PSu dialyzer membranes to improve the efficiency and safety of HD. In the present study, experimental circuits connecting each of the three types of PSu membrane dialyzers that had been sterilized, using gamma irradiation, autoclaving, or in-line steam methods, were prepared. After the dialyzers were primed, saline was circulated in the circuits at a flow rate of 100 mL/min or 200 mL/min. At 0, 2, 4, 6, and 8 h after circulation was initiated, the amount of PVP eluted from the PSu membranes in vitro was determined. In this experimental setting, longer the circulation duration, greater the amount of PVP eluted from the PSu membranes of the tested dialyzers; however, the flow rate did not influence the in vitro elution of PVP. Furthermore, the immersion of the dialyzer membranes in saline for 24 h strongly facilitated the in vitro elution of PVP. In sum, these results suggest that the duration of PSu membrane incubation in saline is a determinant of the level of PVP elution from the PSu membrane dialyzers. 相似文献
37.
Takahide Noguchi Yoshiko Banno Takashi Watanabe Yoshinori Nozawa Yuki Ito 《Mycopathologia》1975,55(2):71-76
In an attempt to evaluate taxonomic character of sugar composition of dermatophytes, the purified cell walls from 13 species are analyzed on neutral sugar composition by gas liquid chromatography. The results were principally compatible with those obtained by conventional morphological examination. Neutral sugar components of dermatophytes cell walls were mannose and glucose in the ratio of 1∶2.7 for Epidermophyton and 1∶1.4 for Microsporum. There were two types in Trichophyton, in which the ratios of mannose to glucose were 1∶1.6 and 1∶3.8. The cases of Trichophyton ferrugineum and Trichophyton mentagrophytes were exceptional. The ratio of the former was 1∶1.4, which implied the relation to Microsporum group, and the ratio of the latter was 1∶2.3, which was supposed to be the intermediate of two types of Trichophyton group. Albino type cell wall of Epidermophyton floccosum was more rich in glucose than pigmented type one. 相似文献
38.
Hiroshi Gomi Satomi Morikawa Naoki Shinmura Hiroaki Moki Tadashi Yasui Azuma Tsukise Seiji Torii Tsuyoshi Watanabe Yoshinori Maeda Masahiro Hosaka 《The journal of histochemistry and cytochemistry》2015,63(5):350-366
The expression of secretogranin III (SgIII) in chicken endocrine cells has not been investigated. There is limited data available for the immunohistochemical localization of SgIII in the brain, pituitary, and pancreatic islets of humans and rodents. In the present study, we used immunoblotting to reveal the similarities between the expression patterns of SgIII in the common endocrine glands of chickens and rats. The protein–protein interactions between SgIII and chromogranin A (CgA) mediate the sorting of CgA/prohormone core aggregates to the secretory granule membrane. We examined these interactions using co-immunoprecipitation in chicken endocrine tissues. Using immunohistochemistry, we also examined the expression of SgIII in a wide range of chicken endocrine glands and gastrointestinal endocrine cells (GECs). SgIII was expressed in the pituitary, pineal, adrenal (medullary parts), parathyroid, and ultimobranchial glands, but not in the thyroid gland. It was also expressed in GECs of the stomach (proventriculus and gizzard), small and large intestines, and pancreatic islet cells. These SgIII-expressing cells co-expressed serotonin, somatostatin, gastric inhibitory polypeptide, glucagon-like peptide-1, glucagon, or insulin. These results suggest that SgIII is expressed in the endocrine cells that secrete peptide hormones, which mature via the intragranular enzymatic processing of prohormones and physiologically active amines in chickens. 相似文献
39.
Narita M Nakajima M Miyoshi K Narita M Nagumo Y Miyatake M Yajima Y Yanagida K Yamazaki M Suzuki T 《Life sciences》2007,80(22):2015-2024
The present study was undertaken to investigate the role of spinal voltage-dependent calcium channel alpha(2)delta-1 subunit in the expression of a neuropathic pain-like state induced by partial sciatic nerve ligation in mice. In cultured spinal neurons, gabapentin (GBP), which displays the inhibitory effect of alpha(2)delta-1 subunit, suppressed the extracellular Ca(2+) influx induced by KCl, whereas it failed to inhibit the intracellular Ca(2+) release induced by inositol-1,4,5-triphosphate. Seven days after sciatic nerve ligation, the protein level of alpha(2)delta-1 subunit in the ipsilateral spinal cord was clearly increased compared to that observed in sham-operated mice. In addition, the mRNA level of alpha(2)delta-1 subunit was significantly increased in the dorsal root ganglion, but not in the spinal cord, of nerve-ligated mice. Under these conditions, a marked decrease in the latency of paw-withdrawal against a thermal stimulation and tactile stimulation, induced by sciatic nerve ligation was abolished by repeated intrathecal (i.t.) treatment with GBP. Additionally, the persistent reduction in the nociceptive threshold by i.t. treatment with GBP at the early stage of the neuropathic pain-like state was maintained for 7 days even after GBP withdrawal. It is of interest to note that a single i.t. post-injection of GBP showed a marked and transient inhibitory effect on the developed neuropathic pain-like state, whereas repeated i.t. post-treatment with GBP produced a persistent inhibitory effect during the treatment. In conclusion, we propose here that the neuropathic pain-like state with sciatic nerve ligation is associated with the increased level of the alpha(2)delta-1 subunit of Ca(2+) channels at the sensory nerve terminal in the spinal dorsal horn of mice. Furthermore, the present data provide evidence that the neuropathic pain may be effectively controlled by repeated treatment with GBP at the early stage. 相似文献
40.
The genome-wide screening of yeast deletion mutants to identify the genes required for tolerance to ethanol and other alcohols 总被引:1,自引:0,他引:1
A set of homozygous diploid deletion mutants of the yeast Saccharomyces cerevisiae was screened for the genes required for tolerance to aliphatic alcohols. The screen identified 137, 122 and 48 deletion mutants sensitive to ethanol, 1-propanol and 1-pentanol, respectively. A number of the genes required for ethanol tolerance were those also required for tolerance to other alcohols. Numerous mutants with defective genes encoding for vacuolar H+ -ATPase (V-ATPase) were cosensitive to these alcohols. A global screening approach of yeast deletion library mutants was useful in elucidating the mechanisms of alcohol tolerance based on different lipophilicities. 相似文献