全文获取类型
收费全文 | 3183篇 |
免费 | 142篇 |
国内免费 | 1篇 |
专业分类
3326篇 |
出版年
2022年 | 19篇 |
2021年 | 24篇 |
2020年 | 12篇 |
2019年 | 29篇 |
2018年 | 41篇 |
2017年 | 21篇 |
2016年 | 69篇 |
2015年 | 104篇 |
2014年 | 107篇 |
2013年 | 252篇 |
2012年 | 173篇 |
2011年 | 177篇 |
2010年 | 111篇 |
2009年 | 143篇 |
2008年 | 201篇 |
2007年 | 178篇 |
2006年 | 193篇 |
2005年 | 192篇 |
2004年 | 203篇 |
2003年 | 186篇 |
2002年 | 193篇 |
2001年 | 24篇 |
2000年 | 26篇 |
1999年 | 26篇 |
1998年 | 49篇 |
1997年 | 48篇 |
1996年 | 46篇 |
1995年 | 34篇 |
1994年 | 39篇 |
1993年 | 41篇 |
1992年 | 17篇 |
1991年 | 15篇 |
1990年 | 24篇 |
1989年 | 17篇 |
1988年 | 21篇 |
1987年 | 23篇 |
1986年 | 24篇 |
1985年 | 20篇 |
1984年 | 16篇 |
1983年 | 15篇 |
1982年 | 23篇 |
1981年 | 24篇 |
1980年 | 20篇 |
1979年 | 9篇 |
1978年 | 15篇 |
1977年 | 7篇 |
1976年 | 13篇 |
1974年 | 10篇 |
1973年 | 6篇 |
1967年 | 6篇 |
排序方式: 共有3326条查询结果,搜索用时 0 毫秒
41.
T Doi H Tokuda R Matsushima-Nishiwaki N The Cuong Y Kageyama Y Iida A Kondo S Akamatsu T Otsuka H Iida O Kozawa S Ogura 《Prostaglandins, leukotrienes, and essential fatty acids》2012,87(2-3):57-62
We have previously shown that ristocetin, an activator of glycoprotein Ib/IX/V, induces release of soluble CD40 (sCD40) ligand via thromboxane (TX) A(2) production from human platelets. In the present study, we investigated the effect of antithrombin-III (AT-III), an anticoagulant, on the ristocetin-induced glycoprotein Ib/IX/V activation in human platelets. AT-III inhibited ristocetin-stimulated platelet aggregation. The ristocetin-induced production of 11-dehydro-TXB(2), a stable metabolite of TXA(2), and the release of sCD40 ligand were suppressed by AT-III. AT-III also reduced the ristocetin-stimulated secretion of platelet-derived growth factor (PDGF)-AB. AT-III failed to affect U46619-, a TXA(2) receptor agonist, induced levels of p38 mitogen-activated protein kinase phosphorylation or sCD40 ligand release. AT-III reduced the binding of SZ2, a monoclonal antibody to the sulfated sequence in the α-chain of glycoprotein Ib, to the ristocetin-stimulated platelets. These results strongly suggest that AT-III reduced ristocetin-stimulated release of sCD40 ligand due to inhibiting TXA(2) production in human platelets. 相似文献
42.
Genetic disruption of Hoxa3 results in bilateral defects of the common carotid artery, which is derived from the third branchial arch artery. The tunica media of the great arteries derived from the arch arteries is formed by the ectomesenchymal neural crest cells. To examine the etiology of the regression of the third arch artery, we generated Hoxa3 homozygous null mutant embryos that expressed a lacZ marker transgene driven by a connexin43 (Cx43): promoter in the neural crest cells. The expression of -galactosidase in these mouse embryos was examined by both whole-mount X-gal staining and immunohistochemistry with the monoclonal -galactosidase antibody on sections. The migration of neural crest cells from the neural tube to the third branchial arch was not affected in the Hoxa3 homozygotes. The initial formation of the third arch artery was also not disturbed. The artery, however, regressed at embryonic day 11.5 (E11.5), when differentiation of the third pharyngeal arch began. The internal and external carotid arteries arose from the dorsal aorta in E12.5 null mutants, which showed an abnormal persistence of the ductus caroticus. The third pharyngeal arch of wild-type mice fuses with the fourth and second arches at E12.0. In the Hoxa3 null mutants, however, the fusion was delayed, and the hypoplastic third pharyngeal arch was still discerned at E12.5. Moreover, the number of proliferating cells in the third arch of the null mutants was small compared with that in the wild-type. Thus, Hoxa3 is required for the growth and differentiation of the third pharyngeal arch. The defective development of the third pharyngeal arch may induce the anomalies of the carotid artery system. This work was supported in part by a grant (no. 14570026) from the Ministry of Education of Japan to Y.K. 相似文献
43.
Fumiyuki Nakagawa Katsutaro Morino Satoshi Ugi Atsushi Ishikado Keiko Kondo Daisuke Sato Shiho Konno Ken-ichi Nemoto Chisato Kusunoki Osamu Sekine Akihiro Sunagawa Masanori Kawamura Noriko Inoue Yoshihiko Nishio Hiroshi Maegawa 《Biochemical and biophysical research communications》2014
It has recently been reported that expression of heme oxygenase-1 (HO-1) plays a protective role against many diseases. Furthermore, n-3 polyunsaturated fatty acids (PUFAs) were shown to induce HO-1 expression in several cells in vitro, and in a few cases also in vivo. However, very few reports have demonstrated that n-3 PUFAs induce HO-1 in vivo. 相似文献
44.
Cutting edge: a novel Toll/IL-1 receptor domain-containing adapter that preferentially activates the IFN-beta promoter in the Toll-like receptor signaling 总被引:27,自引:0,他引:27
Yamamoto M Sato S Mori K Hoshino K Takeuchi O Takeda K Akira S 《Journal of immunology (Baltimore, Md. : 1950)》2002,169(12):6668-6672
MyD88 is a Toll/IL-1 receptor (TIR) domain-containing adapter common to signaling pathways via Toll-like receptor (TLR) family. However, accumulating evidence demonstrates the existence of a MyD88-independent pathway, which may explain unique biological responses of individual TLRs, particularly TLR3 and TLR4. TIR domain-containing adapter protein (TIRAP)/MyD88 adapter-like, a second adapter harboring the TIR domain, is essential for MyD88-dependent TLR2 and TLR4 signaling pathways, but not for MyD88-independent pathways. Here, we identified a novel TIR domain-containing molecule, named TIR domain-containing adapter inducing IFN-beta (TRIF). As is the case in MyD88 and TIRAP, overexpression of TRIF activated the NF-kappaB-dependent promoter. A dominant-negative form of TRIF inhibited TLR2-, TLR4-, and TLR7-dependent NF-kappaB activation. Furthermore, TRIF, but neither MyD88 nor TIRAP, activated the IFN-beta promoter. Dominant-negative TRIF inhibited TLR3-dependent activation of both the NF-kappaB-dependent and IFN-beta promoters. TRIF associated with TLR3 and IFN regulatory factor 3. These findings suggest that TRIF is involved in the TLR signaling, particularly in the MyD88-independent pathway. 相似文献
45.
Characterization of the cells in the repair tissue of full-thickness articular cartilage defects 总被引:1,自引:0,他引:1
H. Nakajima Tatsuhiko Goto Osamu Horikawa Toshiyuki Kikuchi Masayuki Shinmei 《Histochemistry and cell biology》1998,109(4):331-338
It is well established that a full-thickness articular cartilage defect is repaired with a fibrocartilaginous tissue, cells
of which are derived from undifferentiated mesenchymal stem cells in the bone marrow. To characterize the repair cells biochemically,
full-thickness defects were created in rabbit knee joints and the repair tissues taken at 3, 6, and 12 weeks after surgery.
The repair cells were cultured and examined biochemically to investigate the effects of four exogenous growth factors with
regard to the metabolism of type II collagen and proteoglycans. A significant increase of carboxy-terminal type II procollagen
peptide production was observed in the conditional medium of the repair cells, especially taken at 6 weeks after surgery,
in the presence of each growth factor. Glycosaminoglycan content was also increased and proteoglycan synthesis stimulated.
The repair cells taken at the early stage of the repair process could originally have more activity of type II collagen synthesis,
and the growth factors used could enhance the differentiation of the repair cells in vitro.
Accepted: 3 November 1997 相似文献
46.
Osamu Nunobiki Daisuke Sano Kyoko Akashi Taro Higashida Toshitada Ogasawara Hikari Akise Shinji Izuma Kiyo Torii Yoshiaki Okamoto Ichiro Tanaka Masatsugu Ueda 《Human cell》2016,29(2):91-95
To investigate the clinical significance of ALDH2 genetic polymorphisms in cervical carcinogenesis. ALDH2 polymorphisms together with human papillomavirus (HPV) types were examined in a total of 195 cervical smear in exfoliated cervical cell samples using Real-Time polymerase chain reaction (PCR) System. The frequency for the AG+AA genotype was seven in the normal group (70.0 %), 16 in the LSIL group (57.1 %), and 27 in the HSIL group (90.0 %). A significant difference was found between the LSIL and HSIL groups (P = 0.0064). Patients with HSIL lesions frequently had high-risk HPV infections and concurrently belonged to the AG+AA group. ALDH2 genotype in cervical cell samples may be associated with more severe precancerous lesions of the cervix in a Japanese population. 相似文献
47.
Taxonomic characteristics of a strain of thermophilic acidophilic bacillus, Bacillus sp. 11-1S, which had the ability to produce thermophilic acidophilic amylase and thermostable xylanase were examined. Cells of the organism were aerobic, heterotrophic, Gram-positive, spore-forming rods. It grew at temperatures between 45 and 70°C (optimum 65°C) in media of pHs ranging from 2.0 to 5.0 (optimum 3.5 ~ 4.0). Physiological and biochemical characteristics were identical with those of Bacillus acidocaldarius, and % GC of DNA (59%) was close to that of the latter (61 ~ 62%). From these results it was concluded that the organism belongs to B. acidocaldarius Darland and Brock. 相似文献
48.
Expression of a germination-specific amidase, SleB, of Bacilli in the forespore compartment of sporulating cells and its localization on the exterior side of the cortex in dormant spores 下载免费PDF全文
Moriyama R Fukuoka H Miyata S Kudoh S Hattori A Kozuka S Yasuda Y Tochikubo K Makino S 《Journal of bacteriology》1999,181(8):2373-2378
A germination-specific amidase of bacilli is a major spore-lytic enzyme that is synthesized with a putative signal sequence and hydrolyses spore cortex in situ. The sleB gene encoding this amidase in Bacillus subtilis and Bacillus cereus was expressed in the forespore compartment of sporulating cells under the control of sigmaG, as shown by Northern blot and primer extension analyses. The forespore-specific expression of B. subtilis sleB was further indicated by the forespore-specific accumulation of a SleB-green fluorescent protein fusion protein from which a putative secretion signal of SleB was deleted. Immunoelectron microscopy with anti-SleB antiserum and a colloidal gold-immunoglobulin G complex showed that the enzymes from both Bacillus species are located just inside the spore coat layer in the dormant spore, and in the dormant spore, the amidases appear exist in a mature form lacking a signal sequence. These results indicate that SleB is translocated across the forespore's inner membrane by a secretion signal peptide and is deposited in cortex layer synthesized between the forespore inner and outer membranes. The peripheral location of the spore-lytic enzymes in the dormant spore suggests that spore germination is initiated at the exterior of the cortex. 相似文献
49.
Haruhiko Tokuda Jun Kotoyori Atsushi Suzuki Yutaka Oiso Osamu Kozawa 《Journal of cellular biochemistry》1993,52(2):220-226
We investigated the effects of vitamin D3 on the signaling pathways by prostaglandin E2 (PGE2) in osteoblast-like MC3T3-E1 cells. The pretreatment with 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3), an active form of vitamin D3, significantly inhibited cAMP accumulation induced by 10 μM PGE2 in a dose-dependent manner in the range between 1 pM and 1 nM. This effect of 1,25-(OH)2D3 was dependent on the time of pretreatment up to 8 h. 1,25-(OH)2D3 also inhibited the cAMP accumulation induced by NaF, a GTP-binding protein activator, or forskolin which directly activates adenylate cyclase. On the other hand, 1,25-(OH)2D3 significantly inhibited PGE2-induced IP3 formation in a dose-dependent manner between 10 pM and 1 nM. However, 1,25-(OH)2D3 had little effect on NaF-induced IP3 formation. The pretreatment with 24,25-dihydroxyvitamin D3, an inactive form of vitamin D3, affected neither cAMP accumulation nor IP3 formation induced by PGE2. These results strongly suggest that 1,25-(OH)2D3 modulates the signaling by PGE2 in osteoblast-like cells as follows: the inhibitory effect on the cAMP production is exerted at a point downstream from adenylate cyclase and the inhibitory effect on the phosphoinositide hydrolysis is exerted at the point between the PGE2 receptor and GTP-binding protein, probably Gi2. 相似文献
50.
Wong L Lieser SA Miyashita O Miller M Tasken K Onuchic JN Adams JA Woods VL Jennings PA 《Journal of molecular biology》2005,351(1):131-143
The C-terminal Src kinase (Csk) phosphorylates and down-regulates Src family tyrosine kinases. The Csk-binding protein (Cbp) localizes Csk close to its substrates at the plasma membrane, and increases the specific activity of the kinase. To investigate this long-range catalytic effect, the phosphorylation of Src and the conformation of Csk were investigated in the presence of a high-affinity phosphopeptide derived from Cbp. This peptide binds tightly to the SH2 domain and enhances Src recognition (lowers K(m)) by increasing the apparent phosphoryl transfer rate in the Csk active site, a phenomenon detected in rapid quench flow experiments. Previous studies demonstrated that the regulation of Csk activity is linked to conformational changes in the enzyme that can be probed with hydrogen-deuterium exchange methods. We show that the Cbp peptide impacts deuterium incorporation into its binding partner (the SH2 domain), and into the SH2-kinase linker and several sequences in the kinase domain, including the glycine-rich loop in the active site. These findings, along with computational data from normal mode analyses, suggest that the SH2 domain moves in a cantilever fashion with respect to the small lobe of the kinase domain, ordering the active site for catalysis. The binding of a small Cbp-derived peptide to the SH2 domain of Csk modifies these motions, enhancing Src recognition. 相似文献