全文获取类型
收费全文 | 3849篇 |
免费 | 213篇 |
国内免费 | 3篇 |
出版年
2022年 | 23篇 |
2021年 | 50篇 |
2020年 | 25篇 |
2019年 | 45篇 |
2018年 | 48篇 |
2017年 | 58篇 |
2016年 | 83篇 |
2015年 | 125篇 |
2014年 | 142篇 |
2013年 | 252篇 |
2012年 | 243篇 |
2011年 | 252篇 |
2010年 | 171篇 |
2009年 | 170篇 |
2008年 | 233篇 |
2007年 | 236篇 |
2006年 | 223篇 |
2005年 | 237篇 |
2004年 | 207篇 |
2003年 | 195篇 |
2002年 | 201篇 |
2001年 | 51篇 |
2000年 | 39篇 |
1999年 | 60篇 |
1998年 | 37篇 |
1997年 | 44篇 |
1996年 | 36篇 |
1995年 | 27篇 |
1994年 | 25篇 |
1993年 | 38篇 |
1992年 | 44篇 |
1991年 | 48篇 |
1990年 | 36篇 |
1989年 | 44篇 |
1988年 | 29篇 |
1987年 | 21篇 |
1986年 | 29篇 |
1985年 | 25篇 |
1984年 | 27篇 |
1983年 | 25篇 |
1982年 | 31篇 |
1981年 | 20篇 |
1980年 | 13篇 |
1979年 | 12篇 |
1978年 | 11篇 |
1975年 | 6篇 |
1974年 | 16篇 |
1973年 | 9篇 |
1972年 | 6篇 |
1969年 | 5篇 |
排序方式: 共有4065条查询结果,搜索用时 31 毫秒
981.
Miyazawa H Oka-Kira E Sato N Takahashi H Wu GJ Sato S Hayashi M Betsuyaku S Nakazono M Tabata S Harada K Sawa S Fukuda H Kawaguchi M 《Development (Cambridge, England)》2010,137(24):4317-4325
In legumes, the number of symbiotic root nodules is controlled by long-distance communication between the shoot and the root. Mutants defective in this feedback mechanism exhibit a hypernodulating phenotype. Here, we report the identification of a novel leucine-rich repeat receptor-like kinase (LRR-RLK), KLAVIER (KLV), which mediates the systemic negative regulation of nodulation in Lotus japonicus. In leaf, KLV is predominantly expressed in the vascular tissues, as with another LRR-RLK gene, HAR1, which also regulates nodule number. A double-mutant analysis indicated that KLV and HAR1 function in the same genetic pathway that governs the negative regulation of nodulation. LjCLE-RS1 and LjCLE-RS2 represent potential root-derived mobile signals for the HAR1-mediated systemic regulation of nodulation. Overexpression of LjCLE-RS1 or LjCLE-RS2 did not suppress the hypernodulation phenotype of the klv mutant, indicating that KLV is required and acts downstream of LjCLE-RS1 and LjCLE-RS2. In addition to the role of KLV in symbiosis, complementation tests and expression analyses indicated that KLV plays multiple roles in shoot development, including maintenance of shoot apical meristem, vascular continuity, shoot growth and promotion of flowering. Biochemical analyses using transient expression in Nicotiana benthamiana revealed that KLV has the ability to interact with HAR1 and with itself. Together, these results suggest that the potential KLV-HAR1 receptor complex regulates symbiotic nodule development and that KLV is also a key component in other signal transduction pathways that mediate non-symbiotic shoot development. 相似文献
982.
983.
Hiroko Nozaki Yuri Tomoyama Hideyuki Takagi Koutaro Yokoyama Chika Yamada Ken-ichi Kaio Masaki Tsukimori Kazuya Nagao Yuya Itakura Shiori Ohtake-Niimi Hirofumi Nakano Osami Habuchi 《Glycoconjugate journal》2010,27(2):237-248
N-acetylgalactosamine 4-sulfate 6-O-sulfotransferase (GalNAc4S-6ST) transfers sulfate to position 6 of GalNAc(4SO4) residues of chondroitin sulfate to yield chondroitin sulfate E (CS-E). We have previously demonstrated that phenyl-ß-D-GalNAc(4SO4) could serve as an acceptor for GalNAc4S-6ST, thereby inhibiting GalNAc4S-6ST competitively. In this paper we compared the inhibitory effects of various glycosides in which various hydrophobic aglycons were attached to D-GalNAc(4SO4) via ß anomeric configuration. p-Nitrophenyl-ß-D-GalNAc(4SO4) and p-chlorophenyl-ß-D-GalNAc(4SO4) were stronger inhibitors than phenyl-ß-D-GalNAc(4SO4). Among inhibitors examined here, 3-estradiol-ß-D-GalNAc(4SO4) was the strongest inhibitor; the Ki of 3-estradiol-ß-D-GalNAc(4SO4) for the competitive inhibition was 0.008 mM, which was much lower than the Ki of phenyl-ß-D-GalNAc(4SO4), 0.98 mM. In contrast, 7-estradiol-ß-D-GalNAc(4SO4) showed only weak inhibition to GalNAc4S-6ST. 3-Estradiol- ß-D-GalNAc(4SO4) did not inhibit chondroitin 6-sulfotransferase and chondroitin 4-sulfotransferase under the concentration where GalNAc4S-6ST was inhibited by 90%. When 3-estradiol- ß-D-GalNAc(4SO4) was added to the culture medium of chondrosarcoma cells expressing human GalNAc4S-6ST, a significant, albeit small, reduction in the cellular synthesis of CS-E was observed. These results suggest that estradiol group of 3-estradiol-ß-D-GalNAc(4SO4) may enhance the inhibitory activity of the glycoside through increasing the affinity to the enzyme and may allow the glycosides to diffuse at a low efficiency into the cells to inhibit cellular synthesis of CS-E. 相似文献
984.
Sumiya Ishigami Shinichi Ueno Masataka Matsumoto Hiroshi Okumura Takaaki Arigami Yasuto Uchikado Tetsuro Setoyama Hideo Arima Ken Sasaki Masaki Kitazono Hiroyuki Shinchi Yuko Kijima Shoji Natsugoe 《Cancer immunology, immunotherapy : CII》2010,59(3):389-395
Background and aim
A new marker, CD208, was recently explored as a mature interdigitating dendritic cell (DC), and the correlation between the infiltration of CD208-positive cells and clinical factors has been reported in various types of cancers. In this study, we tried to clarify the clinical implication of CD208-positive cell infiltration in gastric cancer immunohistochemically.Patients and methods
A total of 128 gastric cancer patients who underwent a curative operation were enrolled. DCs in tumor nests were identified with two DC markers, CD208 and S-100 protein (S100), by immunohistochemistry. The correlation between clinicopathological features and the CD208- or S100-positive cell infiltration degree was analyzed.Results
Infiltration of S100-positive cells did not correlate with the degree of CD208-positive cell infiltration. Patients with high CD208-positive cell infiltration in the peritumor had a poorer surgical outcome than those with low CD208 infiltration (p < 0.05). Multivariate analysis revealed that CD208-positive cell infiltration was not an independent prognostic factor.Conclusion
We showed that intratumoral CD208-positive cells, as mature DCs, had an inverse correlation to patients’ postoperative outcome in gastric cancer, unlike a conventional DC marker. Evaluation of CD208-positive cell infiltration with S100-positive cell infiltration in gastric cancer is useful to predict antitumor immunological conditions in gastric cancer. 相似文献985.
986.
Akiko Sakata Masaki Mogi Jun Iwanami Kana Tsukuda Li-Juan Min Fei Jing Masaru Iwai Masaharu Ito Masatsugu Horiuchi 《Life sciences》2010,86(17-18):638-645
AimsSex-specific medicine has been highlighted as a different approach to the diagnosis and treatment of diseases between men and women. Type 2 diabetes has been reported to be a risk factor for cognitive impairment. Here, we investigated the sex difference in cognitive function associated with diabetes using KKAy mice.Main methodsCognitive function was evaluated by shuttle avoidance test and Morris water maze test. Changes in gene expression in the brain were evaluated by PCR array and confirmed by quantitative RT-PCR. To evaluate the effect of estradiol, some female KKAy were ovariectomized and treated with or without estradiol.Key findingsIn KKAy mice, female significantly exhibited impaired cognitive function compared with male, while there was no sex difference in these cognitive functions in C57BL6, wild-type mice. Female KKAy mice showed hyperinsulinemia, impaired glucose tolerance and increased oxidative stress compared with male KKAy mice. Female KKAy also showed a significant decrease in peroxisome proliferators-activated receptor (PPAR)-γ expression in the brain compared with male KKAy. Estradiol treatment improved the insulin resistance and higher superoxide production, but failed to improve the cognitive task performance, serum insulin level and lower expression of PPAR-γ.SignificanceIn diabetic mice, female showed significantly impaired cognitive function, with greater insulin resistance, lower expression of PPAR-γ and higher superoxide production compared with male. Estrogen had little effect on cognitive function. These results indicate that a sex-specific approach to cognitive impairment is necessary for diabetic patients, especially for women. 相似文献
987.
Masaki Takahashi Kentarou Ushijima Yohei Hayashi Tomohiro Maekawa Hitoshi Ando Shu-ichi Tsuruoka Akio Fujimura 《Life sciences》2010,86(1-2):24-29
AimsWhile glucocorticoids are widely used to treat patients with various diseases, they often cause adverse effects such as bone fractures. In this study, we investigated whether the decrease in bone density induced by glucocorticoid therapy was ameliorated by optimizing a dosing-time.Main methodsRats were administered with dexamethasone (Dex) orally (1 mg/kg/day) for 6 weeks at a resting or an active period. After the end of the treatment, bone density of femur, biomarkers of bone formation and resorption, and other biomedical variables were measured.Key findingsBone density of femur was significantly decreased by the 6-week treatment with Dex, and the degree of decrease in the 14 HALO (hours after light on) dosing group (an active period) was larger than that in the 2 HALO dosing group (a resting period). Although urinary calcium excretion was accelerated by Dex treatment, secondary hyperparathyroidism was not detected. Histomorphometry analysis showed that Dex suppressed bone resorption, which was larger in the 2 HALO than in the 14 HALO groups. These data indicate that Dex equally suppressed bone formation in the 2 and 14 HALO groups, but inhibited bone resorption more in the 2 HALO than in the 14 HALO groups.SignificanceThis study shows that the decrease in bone density induced by Dex was changed by its dosing-time. 相似文献
988.
Masaki Igarashi Jun-ichi Osuga Masashi Isshiki Motohiro Sekiya Hiroaki Okazaki Satoru Takase Mikio Takanashi Keisuke Ohta Masayoshi Kumagai Makiko Nishi Toshiro Fujita Ryozo Nagai Takashi Kadowaki Shun Ishibashi 《Journal of lipid research》2010,51(2):274-285
Neutral cholesterol ester hydrolase (NCEH) accounts for a large part of the nCEH activity in macrophage foam cells, a hallmark of atherosclerosis, but its subcellular localization and structure-function relationship are unknown. Here, we determined subcellular localization, glycosylation, and nCEH activity of a series of NCEH mutants expressed in macrophages. NCEH is a single-membrane-spanning type II membrane protein comprising three domains: N-terminal, catalytic, and lipid-binding domains. The N-terminal domain serves as a type II signal anchor sequence to recruit NCEH to the endoplasmic reticulum (ER) with its catalytic domain within the lumen. All of the putative N-linked glycosylation sites (Asn270, Asn367, and Asn389) of NCEH are glycosylated. Glycosylation at Asn270, which is located closest to the catalytic serine motif, is important for the enzymatic activity. Cholesterol loading by incubation with acetyl-LDL does not change the ER localization of NCEH. In conclusion, NCEH is targeted to the ER of macrophages, where it hydrolyzes CE to deliver cholesterol for efflux out of the cells. 相似文献
989.
Shinichi Miyamura Shinji Sakaushi Terumitsu Hori Tamotsu Nagumo 《Phycological Research》2010,58(4):258-269
Behaviors of male and female gametes, planozygotes and their microtubular cytoskeletons of a marine green alga Bryopsis maxima Okamura were studied using field emission scanning electron microscopy, high‐speed video microscopy, and anti‐tubulin immunofluorescence microscopy. After fusion of the biflagellate male and female gametes, two sets of basal bodies lay side by side in the planozygote. Four long female microtubular roots extended from the basal bodies to the cell posterior. Four short male roots extended to nearly half the distance to the posterior end. Two flagella, one each from the male and female gametes, become a pair. Specifically, the no. 2 flagellum of the female gamete and one male flagellum point to the right side of the eyespot of the female gamete, which is located at the cell posterior and which is associated with 2s and 2d roots of the female gamete. This spatial relationship of the flagella, microtubular roots, and the eyespot in the planozygote is retained until settlement. During forward swimming, the planozygote swings the flagella backward and moves by flagellar beating. The male and female flagella in the pair usually beat synchronously. The cell withdraws the flagella and becomes round when the planozygote settles to the substratum 20 min after mixing. The axoneme and microtubular roots depolymerize, except for the proximal part and the basal bodies. Subsequently, distinct arrays of cortical microtubules develop in zygotes until 30 min after mixing. These results are discussed with respect to the functional significance of the spatial relationships of flagellar apparatus‐eyespot‐cell fusion sites in the mating gametes and planozygote of green algae. 相似文献
990.
Alam MS Kurabayashi A Hayashi Y Sano N Khan MR Fujii T Sumida M 《Genes & genetic systems》2010,85(3):219-232
We determined the complete nucleotide sequences of mitochondrial (mt) genomes from two dicroglossid frogs, Hoplobatrachus tigerinus (Indian Bullfrog) and Euphlyctis hexadactylus (Indian Green frog). The genome sizes are 20462 bp in H. tigerinus and 20280 bp in E. hexadactylus. Although both genomes encode the typical 37 mt genes, the following unique features are observed: 1) the ND5 genes are duplicated in H. tigerinus that have completely identical sequences, whereas duplicated ND5 genes in E. hexadactylus possessed dissimilar substitutions; 2) duplicated control region (CR) in H. tigerinus has almost identical sequences whereas single control region (CR) was found in E. hexadactylus; 3) the tRNA-Leu (CUN) gene is translocated from the LTPF tRNA cluster to downstream of ND5-1 in H. tigerinus, and the tRNA-Pro gene is translocated from the LTPF tRNA cluster to downstream of CR in E. hexadactylus; 4) pseudo tRNA-Leu (CUN) and tRNA-Pro genes are observed in E. hexadactylus; and 5) two tRNA-Met genes are encoded in both species, as observed in the previously reported dicroglossid mt genomes. Almost all observed gene rearrangements in H. tigerinus and E. hexadactylus can be explained by the tandem duplication and random loss model, except translocation of tRNA-Pro in E. hexadactylus. The novel mt genomic features found in this study may be useful for future phylogenetic studies in the dicroglossid taxa. However, the mt genome with interesting features found in the present study reveal a high level of variation of gene order and gene content, inspiring more research to understand the mechanisms behind gene and genome evolution in the dicroglossid and as well as in the amphibian taxa in future studies. 相似文献