全文获取类型
收费全文 | 2807篇 |
免费 | 142篇 |
国内免费 | 2篇 |
专业分类
2951篇 |
出版年
2024年 | 1篇 |
2023年 | 10篇 |
2022年 | 20篇 |
2021年 | 55篇 |
2020年 | 27篇 |
2019年 | 43篇 |
2018年 | 67篇 |
2017年 | 61篇 |
2016年 | 83篇 |
2015年 | 121篇 |
2014年 | 151篇 |
2013年 | 198篇 |
2012年 | 203篇 |
2011年 | 233篇 |
2010年 | 135篇 |
2009年 | 121篇 |
2008年 | 184篇 |
2007年 | 173篇 |
2006年 | 172篇 |
2005年 | 164篇 |
2004年 | 168篇 |
2003年 | 164篇 |
2002年 | 134篇 |
2001年 | 11篇 |
2000年 | 11篇 |
1999年 | 17篇 |
1998年 | 27篇 |
1997年 | 23篇 |
1996年 | 18篇 |
1995年 | 22篇 |
1994年 | 11篇 |
1993年 | 21篇 |
1992年 | 9篇 |
1991年 | 7篇 |
1990年 | 12篇 |
1989年 | 7篇 |
1988年 | 6篇 |
1987年 | 8篇 |
1986年 | 10篇 |
1985年 | 6篇 |
1984年 | 6篇 |
1983年 | 9篇 |
1982年 | 8篇 |
1981年 | 2篇 |
1980年 | 3篇 |
1979年 | 4篇 |
1976年 | 1篇 |
1975年 | 1篇 |
1974年 | 2篇 |
1973年 | 1篇 |
排序方式: 共有2951条查询结果,搜索用时 0 毫秒
91.
Ecological release is often attributed to the rapid adaptive diversification of phenotypic traits. However, it is not well understood how natural selection changes its strength and direction through the process of ecological release. Herein, we demonstrated how shell colour of the Japanese land snail Euhadra peliomphala simodae has diversified via a shift in natural selection due to ecological release after migration from the mainland to an island. This snail''s shell colour diversified on the island due to disruptive selection after migration from the mainland. We used trail camera traps to identify the cause of natural selection on both the mainland and the island. We then conducted a mark–recapture experiment while collecting microhabitat use data. In total, we captured and marked around 1,700 snails on the mainland, some of which were preyed upon by an unknown predator. The trail camera traps showed that the predator is the large Japanese field mouse Apodemus speciosus, and the predatory frequency was higher on the mainland than on the island. However, this predation did not correlate with shell colour. Microhabitat use on the island was more extensive than on the mainland, with snails on the island using both ground and arboreal microhabitats. A Bayesian estimation showed that the stabilizing selection on shell colour came from factors other than predation. Our results suggest that the course of natural selection was modified due to ecological release after migration from the mainland, explaining one cause of the phenotypic diversification. 相似文献
92.
Umemura YM Vrljic M Nishimura SY Fujiwara TK Suzuki KG Kusumi A 《Biophysical journal》2008,95(1):435-450
Previously, investigations using single-fluorescent-molecule tracking at frame rates of up to 65 Hz, showed that the transmembrane MHC class II protein and its GPI-anchored modified form expressed in CHO cells undergo simple Brownian diffusion, without any influence of actin depolymerization with cytochalasin D. These results are at apparent variance with the view that GPI-anchored proteins stay with cholesterol-enriched raft domains, as well as with the observation that both lipids and transmembrane proteins undergo short-term confined diffusion within a compartment and long-term hop diffusion between compartments. Here, this apparent discrepancy has been resolved by reexamining the same paradigm, by using both high-speed single-particle tracking (50 kHz) and single fluorescent-molecule tracking (30 Hz). Both molecules exhibited rapid hop diffusion between 40-nm compartments, with an average dwell time of 1-3 ms in each compartment. Cytochalasin D hardly affected the hop diffusion, consistent with previous observations, whereas latrunculin A increased the compartment sizes with concomitant decreases of the hop rates, which led to an ∼50% increase in the median macroscopic diffusion coefficient. These results indicate that the actin-based membrane skeleton influences the diffusion of both transmembrane and GPI-anchored proteins. 相似文献
93.
The nucleotide sequences of 11 variable gene segments coding for rabbit T-cell receptor beta (Tcrb-V) chains were determined by directly sequencing fragments amplified by the cassette-ligation mediated polymerase chain reaction (CLM-PCR) and by modified anchor PCR without the cloning procedure. The nucleotide sequences in two of these 11 rabbit Tcrb-V gene segments coincided with those in two of the four rabbit Tcrb-V gene segments previously reported; the others have not been described. The percentage similarity of each nucleotide sequence of the 11 rabbit Tcrb-V gene segments was analyzed and the segments were divided into nine families, which were homologous to nine human families (Vb 2, 3, 4, 5, 7, 8, 10, 18, and 22), respectively.The nucleotide sequence data reported in this paper have been submitted to the DDBJ, EMBL, and GenBank nucleotide sequence databases and have been assigned the accession numbers D17416-D17426. 相似文献
94.
Hirotaka Matsuo Tappei Takada Kimiyoshi Ichida Takahiro Nakamura Akiyoshi Nakayama Hiroshi Suzuki 《Nucleosides, nucleotides & nucleic acids》2013,32(12):1117-1128
Recent genome-wide association studies showed that serum uric acid (SUA) levels relate to ABCG2/BCRP gene, which locates in a gout-susceptibility locus revealed by a genome-wide linkage study. Together with the ABCG2 characteristics, we hypothesized that ABCG2 transports urate and its dysfunction causes hyperuricemia and gout. Transport assays showed ATP-dependent transport of urate via ABCG2. Kinetic analysis revealed that ABCG2 mediates high-capacity transport of urate (Km: 8.24 ± 1.44 mM) even under high-urate conditions. Mutation analysis of ABCG2 in 90 Japanese hyperuricemia patients detected six nonsynonymous mutations, including five dysfunctional variants. Two relatively frequent dysfunctional variants, Q126X and Q141K, were then examined. Quantitative trait locus analysis of 739 Japanese individuals showed that Q141K increased SUA as the number of minor alleles of Q141K increased (p = 6.60 × 10?5). Haplotype frequency analysis revealed that there is no simultaneous presence of Q126X and Q141K in one haplotype. Becuase Q126X and Q141K are assigned to nonfunctional and half-functional haplotypes, respectively, their genotype combinations are divided into four functional groups. The association study with 161 male gout patients and 865 male controls showed that all of those with dysfunctional ABCG2 increased the gout risk, especially those with ≤1/4 function (OR, 25.8; 95% CI, 10.3–64.6; p = 3.39 × 10?21). These genotypes were found in 10.1% of gout patients, but in only 0.9% of control. Our function-based clinicogenetic (FBCG) analysis showed that combinations of the two dysfunctional variants are major causes of gout, thereby providing a new approach for prevention and treatment of the gout high-risk population. 相似文献
95.
Ohno F Watanabe J Sekihara H Hirabayashi T Arata S Kikuyama S Shioda S Nakaya K Nakajo S 《Regulatory peptides》2005,126(1-2):115-122
We have found that pituitary adenylate cyclase-activating polypeptide (PACAP) employed at the physiological concentrations induces the differentiation of mouse neural stem cells into astrocytes. The differentiation process was not affected by cAMP analogues such as dibutylic cAMP (db-cAMP) or 8Br-cAMP or by the specific competitive inhibitor of protein kinase A, Rp-adenosine-3',5'-cyclic monophosphothioate triethylamine salt (Rp-cAMP). Expression of the PACAP receptor (PAC1) in neural stem cells was detected by both RT-PCR and immunoblot using an affinity-purified antibody. The PACAP selective antagonist, PACAP(6-38), had an inhibitory effect on the PACAP-induced differentiation of neural stem cells into astrocytes. These results indicate that PACAP acts on the PAC1 receptor on the plasma membrane of mouse neural stem cells, with the signal then transmitted intracellularly via a PAC1-coupled G protein, does not involve Gs. This signaling mechanism may thus play a crucial role in the differentiation of neural stem cells into astrocytes. 相似文献
96.
Take Matsuyama Takahiro Yamashita Hiroo Imai Yoshinori Shichida 《The Journal of biological chemistry》2010,285(11):8114-8121
Rhodopsin is an extensively studied member of the G protein-coupled receptors (GPCRs). Although rhodopsin shares many features with the other GPCRs, it exhibits unique features as a photoreceptor molecule. A hallmark in the molecular structure of rhodopsin is the covalently bound chromophore that regulates the activity of the receptor acting as an agonist or inverse agonist. Here we show the pivotal role of the covalent bond between the retinal chromophore and the lysine residue at position 296 in the activation pathway of bovine rhodopsin, by use of a rhodopsin mutant K296G reconstituted with retinylidene Schiff bases. Our results show that photoreceptive functions of rhodopsin, such as regiospecific photoisomerization of the ligand, and its quantum yield were not affected by the absence of the covalent bond, whereas the activation mechanism triggered by photoisomerization of the retinal was severely affected. Furthermore, our results show that an active state similar to the Meta-II intermediate of wild-type rhodopsin did not form in the bleaching process of this mutant, although it exhibited relatively weak G protein activity after light irradiation because of an increased basal activity of the receptor. We propose that the covalent bond is required for transmitting structural changes from the photoisomerized agonist to the receptor and that the covalent bond forcibly keeps the low affinity agonist in the receptor, resulting in a more efficient G protein activation. 相似文献
97.
98.
99.
The genes in Butyrivibrio fibrisolvens that encode the enzymes involved in butyrate production were sequenced. In a type I strain (ATCC 19171(T)), the genes coding for the enzymes that catalyze the conversion from acetyl-CoA to butyryl-CoA, thl (thiolase), crt (crotonase), hbd (beta-hydroxybutyryl-CoA dehydrogenase), bcd (butyryl-CoA dehydrogenase), etfB (electron transfer flavoprotein [ETF]-beta), and etfA (ETF-alpha), were found to be clustered and arranged in this order. A type II strain (ATCC 51255) had the same clustered genes with the same arrangement, except that crt was not present in the clustered genes. The deduced amino acid sequences of these enzymes did not greatly differ between the two strains, and even between B. fibrisolvens and clostridia. Amino acid identity appeared to be higher within the same type than between types I and II. The clustered genes were shown to be cotranscribed, and constitutively transcribed without being affected significantly by culture conditions. 相似文献
100.
Yamazaki D Tabara Y Kita S Hanada H Komazaki S Naitou D Mishima A Nishi M Yamamura H Yamamoto S Kakizawa S Miyachi H Yamamoto S Miyata T Kawano Y Kamide K Ogihara T Hata A Umemura S Soma M Takahashi N Imaizumi Y Miki T Iwamoto T Takeshima H 《Cell metabolism》2011,14(2):231-241
TRIC channel subtypes, namely TRIC-A and TRIC-B, are intracellular monovalent cation channels postulated to mediate counter-ion movements facilitating physiological Ca(2+) release from internal stores. Tric-a-knockout mice developed hypertension during the daytime due to enhanced myogenic tone in resistance arteries. There are two Ca(2+) release mechanisms in vascular smooth muscle cells (VSMCs); incidental opening of ryanodine receptors (RyRs) generates local Ca(2+) sparks to induce hyperpolarization, while agonist-induced activation of inositol trisphosphate receptors (IP(3)Rs) evokes global Ca(2+) transients causing contraction. Tric-a gene ablation inhibited RyR-mediated hyperpolarization signaling to stimulate voltage-dependent Ca(2+) influx, and adversely enhanced IP(3)R-mediated Ca(2+) transients by overloading Ca(2+) stores in VSMCs. Moreover, association analysis identified single-nucleotide polymorphisms (SNPs) around the human TRIC-A gene that increase hypertension risk and restrict the efficiency of antihypertensive drugs. Therefore, TRIC-A channels contribute to maintaining blood pressure, while TRIC-A SNPs could provide biomarkers for constitutional diagnosis and personalized medical treatment of essential hypertension. 相似文献