全文获取类型
收费全文 | 4763篇 |
免费 | 538篇 |
国内免费 | 398篇 |
出版年
2024年 | 6篇 |
2023年 | 72篇 |
2022年 | 91篇 |
2021年 | 252篇 |
2020年 | 174篇 |
2019年 | 238篇 |
2018年 | 208篇 |
2017年 | 133篇 |
2016年 | 200篇 |
2015年 | 330篇 |
2014年 | 375篇 |
2013年 | 416篇 |
2012年 | 467篇 |
2011年 | 399篇 |
2010年 | 259篇 |
2009年 | 236篇 |
2008年 | 246篇 |
2007年 | 198篇 |
2006年 | 191篇 |
2005年 | 181篇 |
2004年 | 162篇 |
2003年 | 120篇 |
2002年 | 130篇 |
2001年 | 96篇 |
2000年 | 68篇 |
1999年 | 64篇 |
1998年 | 39篇 |
1997年 | 14篇 |
1996年 | 17篇 |
1995年 | 17篇 |
1994年 | 10篇 |
1993年 | 12篇 |
1992年 | 32篇 |
1991年 | 27篇 |
1990年 | 19篇 |
1989年 | 20篇 |
1988年 | 21篇 |
1987年 | 14篇 |
1986年 | 15篇 |
1985年 | 14篇 |
1984年 | 12篇 |
1983年 | 12篇 |
1982年 | 10篇 |
1981年 | 7篇 |
1980年 | 7篇 |
1979年 | 10篇 |
1978年 | 6篇 |
1975年 | 7篇 |
1974年 | 9篇 |
1972年 | 5篇 |
排序方式: 共有5699条查询结果,搜索用时 31 毫秒
1.
2.
Caveolin induces membrane curvature and drives the formation of caveolae that participate in many crucial cell functions such as endocytosis. The central portion of caveolin-1 contains two helices (H1 and H2) connected by a three-residue break with both N- and C-termini exposed to the cytoplasm. Although a U-shaped configuration is assumed based on its inaccessibility by extracellular matrix probes, caveolin structure in a bilayer remains elusive. This work aims to characterize the structure and dynamics of caveolin-1 (D82–S136; Cav182–136) in a DMPC bilayer using NMR, fluorescence emission measurements, and molecular dynamics simulations. The secondary structure of Cav182–136 from NMR chemical shift indexing analysis serves as a guideline for generating initial structural models. Fifty independent molecular dynamics simulations (100 ns each) are performed to identify its favorable conformation and orientation in the bilayer. A representative configuration was chosen from these multiple simulations and simulated for 1 μs to further explore its stability and dynamics. The results of these simulations mirror those from the tryptophan fluorescence measurements (i.e., Cav182–136 insertion depth in the bilayer), corroborate that Cav182–136 inserts in the membrane with U-shaped conformations, and show that the angle between H1 and H2 ranges from 35 to 69°, and the tilt angle of Cav182–136 is 27 ± 6°. The simulations also reveal that specific faces of H1 and H2 prefer to interact with each other and with lipid molecules, and these interactions stabilize the U-shaped conformation. 相似文献
3.
Wu Changwei W. Tsai Pei-Jung Chen Sharon Chia-Ju Li Chia-Wei Hsu Ai-Ling Wu Hong-Yi Ko Yu-Ting Hung Pai-Chuan Chang Chun-Yen Lin Ching-Po Lane Timothy J. Chen Chia-Yuen 《Sleep and biological rhythms》2019,17(4):423-431
Sleep and Biological Rhythms - Neurovascular coupling (NVC), the transient regional hyperemia following the evoked neuronal responses, is the basis of blood oxygenation level-dependent techniques... 相似文献
4.
James K. Nuñez Jin Chen Greg C. Pommier J. Zachery Cogan Joseph M. Replogle Carmen Adriaens Gokul N. Ramadoss Quanming Shi King L. Hung Avi J. Samelson Angela N. Pogson James Y.S. Kim Amanda Chung Manuel D. Leonetti Howard Y. Chang Martin Kampmann Bradley E. Bernstein Volker Hovestadt Jonathan S. Weissman 《Cell》2021,184(9):2503-2519.e17
5.
William J. Joiner Eliot B. Friedman Hsiao-Tung Hung Kyunghee Koh Mallory Sowcik Amita Sehgal Max B. Kelz 《PLoS genetics》2013,9(9)
A robust, bistable switch regulates the fluctuations between wakefulness and natural sleep as well as those between wakefulness and anesthetic-induced unresponsiveness. We previously provided experimental evidence for the existence of a behavioral barrier to transitions between these states of arousal, which we call neural inertia. Here we show that neural inertia is controlled by processes that contribute to sleep homeostasis and requires four genes involved in electrical excitability: Sh, sss, na and unc79. Although loss of function mutations in these genes can increase or decrease sensitivity to anesthesia induction, surprisingly, they all collapse neural inertia. These effects are genetically selective: neural inertia is not perturbed by loss-of-function mutations in all genes required for the sleep/wake cycle. These effects are also anatomically selective: sss acts in different neurons to influence arousal-promoting and arousal-suppressing processes underlying neural inertia. Supporting the idea that anesthesia and sleep share some, but not all, genetic and anatomical arousal-regulating pathways, we demonstrate that increasing homeostatic sleep drive widens the neural inertial barrier. We propose that processes selectively contributing to sleep homeostasis and neural inertia may be impaired in pathophysiological conditions such as coma and persistent vegetative states. 相似文献
6.
Mutations were induced in tissue-cultured wasabi (Wasabia japonica Matsumura) by treating in vitro-derived shoot tips with either γ-rays or X-rays at 0, 10, 20, 40 or 80 Gy. Doses of up to 40 Gy of either γ- or X-ray treatments
resulted in a survival rate of more than 60% in culture after 3 mo. The use of γ- or X-rays at doses between 10 Gy and 40 Gy
to induce mutation in W. japonica resulted in an alteration of the growth and allyl isothiocyanate (AITC) content of multiple shoots after 3 mo. in culture
on Murashige and Skoog medium containing 5 μM N6-benzyladenine (BA). Putative mutants from the 40 Gy treatments of either γ- or X-rays exhibited a reduction in shoot weight,
number, and height, whereas treatments of either γ-rays or X-rays at 10 Gy and 20 Gy doses showed no significant differences
in shoot growth. All shoots treated with 80 Gy were either necrotic or irregenerable, while those treated with 40 Gy produced
deformed leaves, from both types of ionizing radiation. Concentrations of AITC were measured by the use of gas chromatography-mass
spectrometry (GC-MS). The accumulation of AITC was shown to decrease when doses increased in both γ- and X-ray treatments,
compared with the controls. Positive responses were solely occurred at 18 mo. after transfer of in vitro rooted shoots to the shade house. The survival rate, rhizome weight and AITC content of plants derived from shoots treated
with 20 Gy or 40 Gy of either γ-rays or X-rays were significantly greater than those of the controls. 相似文献
7.
S.C. Hung N.I. Ghali D.L. Venton G.C. Le Breton 《Prostaglandins & other lipid mediators》1982,24(2):195-206
The effects of prostaglandin F2α on human blood platelet function were investigated. PGF2α at 15 μM completely blocked platelet aggregation induced by 500 μM arachidonic acid or 3 μM U46619 but had no effect on aggregatin induced by 7.5 μM ADP. A similar specificity of action was not obtained with either PGI2 or PGE2. Thus concentrations of PGI2 (3 nM) or PGE2 (20 μ M) which inhibited U46619-induced aggregation by 100% also blocked ADP-stimulated aggregation.The inhibitory properties of PGF2α were not related to increases in platelet cAMP, since direct measurement of intracellular cAMP revealed that 15 μ M PGF2α produced no substantial change in cAMP levels. This finding was in direct contrast to results obtained using either PGI2 or PGE2. Both PGI2 (3 nM) and PGE2 (20 μ M) induced significant increases in platelet cAMP levels.The possibility that PGF2α directly interacts at the platelet TXA2/PGH2 receptor was investigated by measuring [3H]PGF2α binding to isolated platelet membranes. It was found that [3H] PGF2α binding reached equilibrium within 30 min at room temperature and could be 90% displaced by addition of 1000 fold excess of unlabelled PGF2α. Furthermore, when 1000 fold excess of either the TXA2/PGH2 “mimetic” U46619 or the TXA2/PGH2 antagonist 13-azaprostanoic acid was added, specific [3H] PGF2α binding was displaced by 95% and 85% respectively. In contrast, the same molar excess of 6-keto-PGF1α, azo analog 1, or TXB2, caused displacement of only 15%, 20% or 25% of the [3H] PGF2α binding. Scatchard analysis indicated that [3H] PGF2α has two binding sites; i.e., a high affinity binding site with an apparent Kd of 50 nM and a low affinity binding site with apparent Kd of 320 nM. These results suggest that the selective inhibition by PGF2α of AA or U46619-induced aggregation may be mediated through interaction at the platelet TXA2/PGH2 receptor. 相似文献
8.
T.‐H. Yen Y. Chen J.‐F. Fu C.‐H. Weng Y.‐C. Tian C.‐C. Hung J.‐L. Lin C.‐W. Yang 《Cell proliferation》2010,43(3):287-296
Objectives: Myofibroblasts are a vital component of stroma of many malignant neoplasms, but it is not yet established whether stromal myofibroblasts also exist in benign tumours such as oncocytoma of the kidney. Materials and methods: Histomorphological and immunohistochemical analysis of 16 renal oncocytomas diagnosed at Chang Gung Memorial Hospital, Taiwan, has been performed. Results: Renal oncocytomas were composed of oncocytes, large cells with granular eosinophilic cytoplasm, arranged mostly in sheets, in tubulocystic or combined pattern. Few oncocytes appeared to be undergoing proliferation or apoptosis. MIB‐1 and active caspase 3 indices were low, but higher in tumour than in surrounding non‐tumour parenchyma (MIB‐1: 0.93 ± 0.09 versus 0.46 ± 0.07, P < 0.001 and active caspase 3: 0.76 ± 0.08 versus 0.41 ± 0.09, P < 0.001). Wnt/β‐catenin signalling was not implicated in this neoplasm, as there was no loss of E‐cadherin membranous localization or expression of intranuclear β‐catenin in the cells. Clumps of oncocytes were stained with periodic acid Schiff and had collagen I‐, collagen III‐ and fibronectin‐positive, but desmin‐ and human caldesmon‐negative stromas. Importantly, α‐smooth muscle actin (SMA)‐immunostaining established the myofibroblastic nature of many of the stromal cells. Some of the myofibroblasts were also positive for MIB‐1, indicating a proliferative role for them in the stroma. Conclusions: Renal oncocytomas were composed of two independent compartments: benign oncocytes and pronounced fibrotic stroma, which consisted of proliferating myofibroblasts (SMA‐ and MIB‐1‐positive) which were associated with excessive deposition of extracellular matrix (periodic acid Schiff‐component, collagen I‐, collagen III‐ and fibronectin‐positive, and desmin‐ and human caldesmon‐negative). 相似文献
9.
10.
Ya‐Yun Zuo Huan‐Huan Ma Wen‐Jie Lu Xing‐Liang Wang Shu‐Wen Wu Ralf Nauen Yi‐Dong Wu Yi‐Hua Yang 《Insect Science》2020,27(4):791-800
Insect ryanodine receptors (RyRs) are the targets of diamide insecticides. Two point mutations G4946E and I4790M (numbering according to Plutella xylostella, PxRyR) in the transmembrane domain of the insect RyRs associated with diamide resistance have so far been identified in three lepidopteran pests, P. xylostella, Tuta absoluta and Chilo suppressalis. In this study, we identified one of the known RyR target site resistance mutations (I4790M) in a field‐collected population of Spodoptera exigua. The field‐collected WF population of S. exigua exhibited 154 fold resistance to chlorantraniliprole when compared with the susceptible WH‐S strain. Sequencing the transmembrane domains of S. exigua RyR (SeRyR) revealed that the resistant WF strain was homozygous for the I4743M mutation (corresponding to I4790M in PxRyR), whereas the G4900E allele (corresponding to G4946E of PxRyR) was not detected. The 4743M allele was introgressed into the susceptible WH‐S strain by crossing WF with WH‐S, followed by three rounds of backcrossing with WH‐S. The introgressed strain 4743M was homozygous for the mutant 4743M allele and shared about 94% of its genetic background with that of the recipient WH‐S strain. Compared with WH‐S, the near‐isogenic 4743M strain showed moderate levels of resistance to chlorantraniliprole (21 fold), cyantraniliprole (25 fold) and flubendiamide (22 fold), suggesting that the I4743M mutation confers medium levels of resistance to all three diamides. Genetic analysis showed diamide resistance in the 4743M strain was inherited as an autosomal and recessive trait. Results from this study have direct implications for the design of appropriate resistance monitoring and management practices to sustainably control S. exigua. 相似文献