全文获取类型
收费全文 | 4569篇 |
免费 | 283篇 |
国内免费 | 3篇 |
出版年
2021年 | 39篇 |
2020年 | 18篇 |
2019年 | 43篇 |
2018年 | 36篇 |
2017年 | 43篇 |
2016年 | 72篇 |
2015年 | 107篇 |
2014年 | 143篇 |
2013年 | 335篇 |
2012年 | 221篇 |
2011年 | 199篇 |
2010年 | 151篇 |
2009年 | 154篇 |
2008年 | 243篇 |
2007年 | 237篇 |
2006年 | 223篇 |
2005年 | 235篇 |
2004年 | 244篇 |
2003年 | 240篇 |
2002年 | 246篇 |
2001年 | 111篇 |
2000年 | 124篇 |
1999年 | 111篇 |
1998年 | 68篇 |
1997年 | 52篇 |
1996年 | 42篇 |
1995年 | 58篇 |
1994年 | 42篇 |
1993年 | 65篇 |
1992年 | 96篇 |
1991年 | 86篇 |
1990年 | 65篇 |
1989年 | 61篇 |
1988年 | 60篇 |
1987年 | 49篇 |
1986年 | 44篇 |
1985年 | 47篇 |
1984年 | 49篇 |
1983年 | 38篇 |
1982年 | 28篇 |
1981年 | 34篇 |
1980年 | 18篇 |
1979年 | 27篇 |
1978年 | 28篇 |
1977年 | 19篇 |
1976年 | 28篇 |
1975年 | 22篇 |
1972年 | 20篇 |
1970年 | 19篇 |
1969年 | 17篇 |
排序方式: 共有4855条查询结果,搜索用时 31 毫秒
11.
Jun Iwaki Kunio Kikuchi Yoshiaki Mizuguchi Yutaka Kawahigashi Hiroshi Yoshida Eiji Uchida Toshihiro Takizawa 《PloS one》2013,8(7)
MicroRNA miR-376c was expressed in normal intrahepatic biliary epithelial cells (HIBEpiC), but was significantly suppressed in the HuCCT1 intrahepatic cholangiocarcinoma (ICC) cell line. The biological significance of the down-regulation of miR-376c in HuCCT1 cells is unknown. We hypothesized that miR-376c could function as a tumor suppressor in these cells. To test this hypothesis, we sought the targets of miR-376c, and characterized the effect of its down-regulation on HuCCT1 cells. We performed proteomic analysis of miR-376c-overexpressing HuCCT1 cells to identify candidate targets of miR-376c, and validated these targets by 3′-UTR reporter assay. Transwell migration assays were performed to study the migratory response of HuCCT1 cells to miR-376c overexpression. Furthermore, microarrays were used to identify the signaling that were potentially involved in the miR-376c-modulated migration of HuCCT1. Finally, we assessed epigenetic changes within the potential promoter region of the miR-376c gene in these cells. Proteomic analysis and subsequent validation assays showed that growth factor receptor-bound protein 2 (GRB2) was a direct target of miR-376c. The transwell migration assay revealed that miR-376c significantly reduced epidermal growth factor (EGF)-dependent cell migration in HuCCT1 cells. DNA microarray and subsequent pathway analysis showed that interleukin 1 beta and matrix metallopeptidase 9 were possible participants in EGF-dependent migration of HuCCT1 cells. Bisulfite sequencing showed higher methylation levels of CpG sites upstream of the miR-376c gene in HuCCT1 relative to HIBEpiC cells. Combined treatment with the DNA-demethylating agent 5-aza-2′-deoxycytidine and the histone deacetylase inhibitor trichostatin A significantly upregulated the expression of miR-376c in HuCCT1 cells. We revealed that epigenetic repression of miR-376c accelerated EGF-dependent cell migration through its target GRB2 in HuCCT1 cells. These findings suggest that miR-376c functions as a tumor suppressor. Since metastasis is the major cause of death in ICC, microRNA manipulation could lead to the development of novel anti-cancer therapy strategies for ICC. 相似文献
12.
13.
Hydrogen peroxide was formed in isolated cell walls from Marchantiapolymorpha L. in the presence of MnCl2 by either NADH or NADPHoxidation. This reaction was stimulated by phenols such as 2,4-dichlorophenolor p-coumarate, suggesting a reaction similar to that proposedfor the last step of lignification in higher plant cells, althoughbryophytes have been reported to be devoid of lignin. (Received June 16, 1987; Accepted March 3, 1987) 相似文献
14.
Kinetics of the change of photosystem (PS) composition in cyanobacteriainduced by chromatic light were studied in relation to cellproliferation. The study was made for two unicellular strains,Synechococcus NIBB 1059 and Synechocystis (Aphanocapsa) PCC6714. We found that (1) the change to a higher or lower PS I/IIratio was due to acceleration or suppression of apparent PSI formation, and (2) it progressed on a similar time scale tothat of the cell proliferation. The apparent rate constant ofthe change in the PS I/II ratio was proportional to that ofcell proliferation, µ, when this was low, but at highvalues of µ the increase in the rate constant of the changein the PS I/II ratio became smaller, causing a deviation fromthe linear relationship. Results indicate that under autotrophicconditions, the photoregulated composition change occurs asa result of thylakoid development, which accompanies cell proliferation. (Received June 23, 1986; Accepted December 5, 1986) 相似文献
15.
The characteristics of phosphate transport across intestinal basolateral membranes of the rat were determined by using enriched preparations in which uphill Na+-dependent D-glucose transport could not be demonstrated, but ATP-dependent Ca2+ transport was present. Phosphate transport was saturable, Na+-dependent and exhibited Michaelis-Menten kinetics. Vmax. was 51.1 +/- 4.2 pmol/10 s per mg of protein and Km was 14 +/- 3.9 microM. The transport process was electroneutral. Tracer-exchange experiments and counter-transport studies confirmed the presence of a Na+-Pi carrier at the basolateral membrane. The presence of inside-positive membrane potential did not enhance phosphate uptake, indicating that the Na+ effect is secondary to the presence of the Na+-Pi carrier rather than an induction of positive membrane potential. The stoichiometry of this carrier at pH 7.4 was 2 Na+:1 phosphate, as shown by direct studies utilizing the static-head method. These studies are the first to determine the presence of a phosphate carrier at the basolateral membrane. 相似文献
16.
Genetic mechanisms of tumor-specific loss of 11p DNA sequences in Wilms tumor. 总被引:12,自引:7,他引:5 下载免费PDF全文
D D Dao W T Schroeder L Y Chao H Kikuchi L C Strong V M Riccardi S Pathak W W Nichols W H Lewis G F Saunders 《American journal of human genetics》1987,41(2):202-217
Wilms tumor, a common childhood renal tumor, occurs in both a heritable and a nonheritable form. The heritable form may occasionally be attributed to a chromosome deletion at 11p13, and tumors from patients with normal constitutional chromosomes often show deletion or rearrangement of 11p13. It has been suggested that a germinal or somatic mutation may occur on one chromosome 11 and predispose to Wilms tumor and that a subsequent somatic genetic event on the normal homologue at 11p13 may permit tumor development. To study the frequency and mechanism of such tumor-specific genetic events, we have examined the karyotype and chromosome 11 genotype of normal and tumor tissues from 13 childhood renal tumor patients with different histologic tumor types and associated clinical conditions. Tumors of eight of the 12 Wilms tumor patients, including all viable tumors examined directly, show molecular evidence of loss of 11p DNA sequences by somatic recombination (four cases), chromosome loss (two cases), and recombination (two cases) or chromosome loss and duplication. One malignant rhabdoid tumor in a patient heterozygous for multiple 11p markers did not show any tumor-specific 11p alteration. These findings confirm the critical role of 11p sequences in Wilms tumor development and reveal that mitotic recombination may be the most frequent mechanism by which tumors develop. 相似文献
17.
Takuo Yamakura Akio Hagihara Sukristijono Sukardjo Husato Ogawa 《Ecological Research》1987,2(3):215-227
The form of tropical trees was studied with reference to the production structure of the component individuals of a tropical
rain forest stand in Sebulu, East Kalimantan in Indonesian Borneo, since the production structure as a physical or bio-economical
basis of tree form still remains obscure in tropical rain forests. The pipe model theory successfully explained the crown
shapes of different trees, and its parameter, designated as specific pipe length, suggested an increase in the cost of leaf
mass growth with an increase in crown size. A mathematical model consisting of exponential functions of aboveground height
was applied for describing stem form, and its properties were examined through changes in its coefficients and by adopting
an assumption of the geometrical similarity of individual stem form as a criterion for comparing differences in stem form
among individual trees. Furthermore, the cost of buttersses was discussed using the relation between bole- and buttress weight
calculated from the mathematical model. 相似文献
18.
Junichi Ishihara Nagahiro Saijo Yasutsuna Sasaki Hidehiko Nakano Akira Ozaki Hidenobu Takahashi Masanori Sakurai Kazuhiko Nakagawa Masaaki Iigo Fumihiko Kanzawa Akio Hoshi Weon Seon Hong James R. Jett Terumi Takahashi 《Cancer immunology, immunotherapy : CII》1987,24(3):185-189
Summary The antitumor effect of recombinant human tumor necrosis factor (rH-TNF) on two clones of rat fibrosarcoma with different metastatic potential to lymph nodes was examined. The colony formation of clone A, which has high metastatic potential, was completely inhibited by continuous exposure to rH-TNF at 50 U/ml. In contrast, colony formation of clone G, which has low metastatic potential, was not inhibited by high concentrations of rH-TNF (10,000 U/ml). The inhibitory effect of rH-TNF on colony formation by clone A was also observed with a 1-h exposure to rH-TNF. This effect was time and concentration dependent, as determined by the colony assay, 3H-thymidine uptake assay, and 51Cr-release assay. 3H-thymidine and 3H-uridine uptake per cell of clone A exposed to rH-TNF was not decreased. This suggests that the mechanisms of the antitumor effect of rH-TNF were not due to inhibition of DNA and RNA synthesis of tumor cells. In vivo growth and lymph node metastases of clone A inoculated i.p. to Donryu strain rats were completely suppressed by 14 consecutive i.p. injections of 105 or 106 U/kg per day of rH-TNF. On the other hand the growth of clone G was not influenced by rH-TNF administration. 相似文献
19.
The changes of dominance rank among female Japanese monkeys of the Koshima group over a period of 29 years from 1957 were
studied. The dominance rank order was relatively stable in the early population growing phase, while large scale-changes of
dominance rank order occurred successively in the phase of population decrease brought about by the severe control of artificial
feeding after 1972. Nevertheless, the rank order of several females of the highest status was stable. Furthermore, the reproductive
success of these highest status females was high (Mori, 1979a;Watanabe et al., in prep.). Divergence of the dominance rank order fromKawamura's rules (Kawamura, 1958) was observed in the following respects: (1) Some females significantly elevated their rank depending on the leader
males. (2) If mothers died when their daughters were still juveniles or nulliparous, the dominance rank of some of these offspring
females was significantly lower than the mother's one. However 55% of daughters which lost their mothers at a young age inherited
the mother's rank. (3) Dominance among sisters whose mother had died when at least one of the daughters was under 6 years
old followed the rule of youngest ascendancy in 60% (Kawamura, 1958), and in 80% when both of the daughters were nulliparous at the mother's death.
The mean rate of aggressive interactions for each female with subordinates to her was calculated by dividing the total aggressive
interactions between the female in question and her subordinates by the number of subordinate females to the female in question.
A female which showed a high rate of aggressive interactions with her subordinates was categorized as an “Attacker”, and a
female showing a lower rate was categorized as a “Non-attacker”. Similarly, categories of “Attacked”, and “Non-attacked” were
distinguished by using the rate of aggressive interactions with dominant females. Several females which were once categorized
in one category in a year were repeatedly categorized in the same category over different years. The “Attacked” tended to
be females of higher rank, and “Non-attackers” tended to be females of lower rank. “The second-higher-status females”, were
“Attacked”, and their rank was unstable. In particular, females of lower rank within the lineage of the highest rank suffered
this kind of severe status. Most of the daughters of these females showed a sharp drop of rank, and died when they were still
at a young age, i.e. “the second-higher-status females” displayed low fitness. “Non-attackers” were significantly “Non-attacked”;
i.e. they were females which showed a non-social attitude. Females which underwent a drop of rank tended to be “Non-attackers”.
The most important factor which determined the females' rank was the memory of their dominance relations under the influence
of their mother [dependent rank (Kawai, 1958)] in their early life during development. This finding corresponds well with the results in baboons obtained byWalter (1980); the target females of aggressive interactions by adolescent females were determined by the rank of the mothers when
these adolescent females were born. 相似文献
20.
K Sano A Kikuchi Y Matsui Y Teranishi Y Takai 《Biochemical and biophysical research communications》1989,158(2):377-385
We have purified a novel GTP-binding protein, designated as the smg-25A protein (smg p25A), from bovine brain membranes and determined its primary structure. In the present studies, the smg-25A mRNA levels in various tissues have been studied. The 1.6-kilobase smg-25A mRNA is detected in rat brain by Northern blot analysis. This mRNA is not detected in other rat tissues including thymus, lung, heart, liver, small intestine, kidney, and skeletal muscle. The 1.6-kilobase smg-25A mRNA is also detected in bovine adrenal medulla but not in the cortex. Moreover, this mRNA is detected in rat pheochromocytoma PC-12 cells and its level increases after differentiation of the cells into sympathetic neuron-like cells in response to nerve growth factor or dibutyryl cyclic AMP. This mRNA level does not increase in response to 12-O-tetradecanoylphorbol-13-acetate incapable of inducing differentiation. These results suggest that the smg-25A gene is specifically expressed in nerve tissues and that smg p25A plays a role in some neuronal functions. 相似文献