全文获取类型
收费全文 | 1581篇 |
免费 | 104篇 |
专业分类
1685篇 |
出版年
2023年 | 10篇 |
2022年 | 5篇 |
2021年 | 17篇 |
2020年 | 7篇 |
2019年 | 16篇 |
2018年 | 15篇 |
2017年 | 13篇 |
2016年 | 27篇 |
2015年 | 43篇 |
2014年 | 57篇 |
2013年 | 87篇 |
2012年 | 74篇 |
2011年 | 77篇 |
2010年 | 57篇 |
2009年 | 44篇 |
2008年 | 85篇 |
2007年 | 82篇 |
2006年 | 86篇 |
2005年 | 76篇 |
2004年 | 61篇 |
2003年 | 80篇 |
2002年 | 58篇 |
2001年 | 55篇 |
2000年 | 55篇 |
1999年 | 50篇 |
1998年 | 16篇 |
1997年 | 19篇 |
1996年 | 15篇 |
1995年 | 14篇 |
1994年 | 10篇 |
1993年 | 15篇 |
1992年 | 38篇 |
1991年 | 46篇 |
1990年 | 26篇 |
1989年 | 28篇 |
1988年 | 22篇 |
1987年 | 22篇 |
1986年 | 26篇 |
1985年 | 19篇 |
1984年 | 18篇 |
1983年 | 19篇 |
1982年 | 10篇 |
1981年 | 9篇 |
1979年 | 5篇 |
1977年 | 12篇 |
1976年 | 5篇 |
1975年 | 10篇 |
1974年 | 9篇 |
1973年 | 5篇 |
1968年 | 5篇 |
排序方式: 共有1685条查询结果,搜索用时 15 毫秒
191.
Aiko Nitta Yosuke Iura Hideki Inoue Ippei Sato Koichiro Morihira Hirokazu Kubota Tatsuaki Morokata Makoto Takeuchi Mitsuaki Ohta Shin-ichi Tsukamoto Takayuki Imaoka Toshiya Takahashi 《Bioorganic & medicinal chemistry letters》2012,22(22):6876-6881
Optimization starting with our lead compound 1 (IC50 = 4.9 nM) led to the identification of pyrrolidinyl phenylurea derivatives. Further modification toward improvement of the bioavailability provided (R)-1-(1-((6-fluoronaphthalen-2-yl)methyl)pyrrolidin-3-yl)-3-(2-(2-hydroxyethoxy)phenyl)urea 32 (IC50 = 1.7 nM), a potent and orally active CCR3 antagonist. 相似文献
192.
Tadashi Honjo Satoshi Kubota Hiroshi Kamioka Yasuyo Sugawara Yoshihito Ishihara Takashi Yamashiro Masaharu Takigawa Teruko Takano-Yamamoto 《Journal of cell communication and signaling》2012,6(4):225-232
Fluid flow stress (FSS) is a major mechanical stress that induces bone remodeling upon orthodontic tooth movement, whereas CCN family protein 2 (CCN2) is a potent regenerator of bone defects. In this study, we initially evaluated the effect of laminar FSS on Ccn2 expression and investigated its mechanism in osteoblastic MC3T3-E1 cells. The Ccn2 expression was drastically induced by uniform FSS in an intensity dependent manner. Of note, the observed effect was inhibited by a Rho kinase inhibitor Y27632. Moreover, the inhibition of actin polymerization blocked the FSS-induced activation of Ccn2, whereas inducing F-actin formation using cytochalasin D and jasplakinolide enhanced Ccn2 expression in the same cells. Finally, F-actin formation was found to induce osteoblastic differentiation. In addition, activation of cyclic AMP-dependent kinase, which inhibits Rho signaling, abolished the effect of FSS. Collectively, these findings indicate the critical role of actin polymerization and Rho signaling in CCN2 induction and bone remodeling provoked by FSS. 相似文献
193.
Noji T Miyamoto M Kubota KC Shinohara T Ambo Y Matsuno Y Kashimura N Hirano S 《World journal of surgical oncology》2012,10(1):106
ABSTRACT: BACKGROUND: Lymph node metastasis (LNM) is one of the most important prognostic factors for extra-hepatic bile duct carcinoma (ExHBDC). Extra capsular lymph node involvement (ExCLNI) is the extension of cancer cells through the nodal capsule into the perinodal fatty tissue. The prognostic impact of ExCLNI has been shown to be mainly significant in head and neck malignancies. Recently, the prognostic impacts of ExCLNI have been evaluated in gastrointestinal malignancies. However, no data are available regarding the incidence and prognostic significance of extra-capsular lymph node involvement (ExCLNI) in resectable ExHBDCs. The aim of the present study is first to evaluate the incidence of ExCLNI in surgically-treated ExHBDCs and, second, to determine the prognostic impact of ExCLNI in patients with surgically-treated ExHBDCs. METHODS: A total of 228 patients, (110 cases of hilar cholangiocarcinoma and 118 cases of distal cholangiocarcinoma), with surgically-treated ExHBDCs were included in this retrospective study. ExCLNI was defined as the extension of cancer cells through the nodal capsule into the perinodal fatty tissue. The existence of ExCLNI and its prognostic value were analyzed as a subgroup of lymph node metastasis. RESULTS: ExCLNI was detected in only 22% of patients with lymph node metastasis of surgically-treated ExHBDC. The presence of ExCLNI correlated with distal cholangiocarcinoma (P = 0.002). On univariate analysis for survival, perineural invasion, vascular invasion, histological grade, and lymph node metastasis were statistically significant factors. On multivariate analysis, only lymph node metastasis was identified as a significant independent prognostic factor in patients with resectable ExHBDC. Subgroups of lymph node metastasis including the presence of ExCLNI, location of lymph node metastasis, and the number of lymph node metastasis had no statistically significant impact on survival. CONCLUSION: ExCLNI was present in only 22% of the LNM (7% of overall patients) in patients with surgically-treated ExHBDCs. And ExCLNI would have no impact on the survival of patients with surgically-treated ExHBDCs. 相似文献
194.
Animals recognize biologically relevant sounds, such as the non-harmonic sounds made by some predators, and respond with adaptive behaviors, such as escaping. To clarify which acoustic parameters are used for identifying non-harmonic, noise-like, broadband sounds, guinea pigs were conditioned to a natural target sound by introducing a novel training procedure in which 2 or 3 guinea pigs in a group competed for food. A set of distinct behavioral reactions was reliably induced almost exclusively to the target sound in a 2-week operant training. When fully conditioned, individual animals were separately tested for recognition of a set of target-like sounds that had been modified from the target sound, with spectral ranges eliminated or with fine or coarse temporal structures altered. The results show that guinea pigs are able to identify the noise-like non-harmonic natural sounds by relying on gross spectral compositions and/or fine temporal structures, just as birds are thought to do in the recognition of harmonic birdsongs. These findings are discussed with regard to similarities and dissimilarities to harmonic sound recognition. The results suggest that similar but not identical processing that requires different time scales might be used to recognize harmonic and non-harmonic sounds, at least in small mammals. 相似文献
195.
Pirfenidone inhibits the expression of HSP47 in TGF-beta1-stimulated human lung fibroblasts 总被引:1,自引:0,他引:1
Nakayama S Mukae H Sakamoto N Kakugawa T Yoshioka S Soda H Oku H Urata Y Kondo T Kubota H Nagata K Kohno S 《Life sciences》2008,82(3-4):210-217
Pirfenidone (5-methyl-1-phenyl-2-(1H)-pyridone) is a novel anti-fibrotic and anti-inflammatory agent that inhibits the progression of fibrosis in animal models and patients with idiopathic pulmonary fibrosis (IPF). Heat shock protein (HSP) 47, a collagen-specific molecular chaperone, is involved in the processing and/or secretion of procollagen and plays an important role in the pathogenesis of IPF. The present study evaluated the in vitro effects of pirfenidone on expression of HSP47 and collagen type I in cultured normal human lung fibroblasts (NHLF). Expression levels of HSP47 and collagen type I in NHLF stimulated by transforming growth factor (TGF)-beta1 were evaluated genetically, immunologically and immunocytochemically. Treatment with TGF-beta1 stimulated both mRNA and protein expressions of both HSP47 and collagen type I in NHLF, and pirfenidone significantly inhibited this TGF-beta1-enhanced expression in a dose-dependent manner. We concluded that the anti-fibrotic effect of pirfenidone may be mediated not only through direct inhibition of collagen type I expression but also at least partly through inhibition of HSP47 expression in lung fibroblasts, with a resultant reduction of collagen synthesis in lung fibrosis. 相似文献
196.
We have designed a doubly thiazole orange labeled nucleoside showing high fluorescence intensity for a hybrid with the target DNA and effective quenching for a single-stranded state. Knowing how much the fluorescence emission and quenching of this probe depend on the probe sequence and why there is such a sequence dependence is important for effective probe design, we synthesized more than 30 probe sequences and measured their fluorescence intensities. When the probe hybridized with the target DNA strands, there was strong emission, whereas the emission intensity was much weaker before hybridization; however, self-dimerization of probes suppressed fluorescence quenching. In particular, the G/C base pairs neighboring the labeled nucleotide in a self-dimeric structure resulted in a low quenching ability for the probe before hybridization. On the other hand, mismatched base pair formation around the labeled site decreased the fluorescence intensity because the neighboring sequence is the binding site of the tethered thiazole orange dyes. The hybridization enhanced the fluorescence of the probe even when the labeled nucleotide was located at the end of the probe strand; however, the partial lack of duplex structure resulted in a decrease in the fluorescence intensity of the hybrid. 相似文献
197.
198.
Ken Sasaki Jyoti Gaikwad Shuhei Hashiguchi Toshiya Kubota Kazuhisa Sugimura Werner Kremer Hans Robert Kalbitzer Kazuyuki Akasaka 《朊病毒》2008,2(3):118-122
The structure and the dissociation reaction of oligomers PrPoligo from reduced human prion huPrPC(23–231) have been studied by 1H-NMR and tryptophan fluorescence spectroscopy at varying pressure, along with circular dichroism and atomic force microscopy. The 1H-NMR and fluorescence spectral feature of the oligomer is consistent with the notion that the N-terminal residues including all seven Trp residues, are free and mobile, while residues 105∼210, comprising the AGAAAAGA motif and S1-Loop-HelixA-Loop-S2-Loop-HelixC, are engaged in intra- and/or inter-molecular interactions. By increasing pressure to 200 MPa, the oligomers tend to dissociate into monomers which may be identified with PrPC*, a rare metastable form of PrPC stabilized at high pressure (Kachel et al., BMC Struct Biol 6:16). The results strongly suggest that the oligomeric form PrPoligo is in dynamic equilibrium with the monomeric forms via PrPC*, namely huPrPC ⇆ huPrPC* ⇆ huPrPoligo.Key words: human prion, oligomer structure, pressure dissociation, reversible monomer-oligomer transition, circular dichroism, high pressure NMR, atomic force microscopy 相似文献
199.
Osakabe M Isobe H Kasai A Masuda R Kubota S Umeda M 《Experimental & applied acarology》2008,44(3):165-183
Aerial dispersal may be important for redistribution of spider mites into new habitats. Evidence for behavioral control of
aerial take-off has been well documented for Tetranychus urticae Koch. Before aerial dispersal they exhibit the aerial take-off posture that involves lifting the forelegs upright and raising
the forebody. However, whether the aerial take-off posture functions to increase drag has remained unclear. The objectives
of this study were to clarify: (i) aerodynamic effects of the aerial take-off posture; and (ii) actual aerial take-off behavior
in T. urticae. To evaluate the aerodynamic forces experienced by grounded spider mites in different postures, we constructed three-dimensional
models of T. urticae, exhibiting the aerial take-off posture and the normal posture, using computer graphics. We found that the aerial take-off
posture was effective in receiving greater rearward forces from wind rather than upward forces. As a result, aerial take-off
from a horizontal platform is unlikely. Instead, inverted departure surfaces, e.g., lower leaf surfaces, with inclines are
likely to be effective sites for take-off. Laboratory experiments and field observations indicated that the mites preferentially
adopted such a position for orientation and take-off. Our findings provided a rationale for the take-off behavior of Tetranychus spider mites. 相似文献
200.