全文获取类型
收费全文 | 6227篇 |
免费 | 713篇 |
国内免费 | 189篇 |
专业分类
7129篇 |
出版年
2024年 | 9篇 |
2023年 | 130篇 |
2022年 | 144篇 |
2021年 | 212篇 |
2020年 | 271篇 |
2019年 | 357篇 |
2018年 | 283篇 |
2017年 | 335篇 |
2016年 | 322篇 |
2015年 | 276篇 |
2014年 | 341篇 |
2013年 | 537篇 |
2012年 | 209篇 |
2011年 | 357篇 |
2010年 | 241篇 |
2009年 | 367篇 |
2008年 | 387篇 |
2007年 | 341篇 |
2006年 | 303篇 |
2005年 | 218篇 |
2004年 | 270篇 |
2003年 | 169篇 |
2002年 | 139篇 |
2001年 | 125篇 |
2000年 | 100篇 |
1999年 | 86篇 |
1998年 | 96篇 |
1997年 | 73篇 |
1996年 | 68篇 |
1995年 | 65篇 |
1994年 | 47篇 |
1993年 | 74篇 |
1992年 | 61篇 |
1991年 | 26篇 |
1990年 | 17篇 |
1989年 | 8篇 |
1988年 | 9篇 |
1987年 | 9篇 |
1986年 | 8篇 |
1985年 | 8篇 |
1984年 | 6篇 |
1983年 | 4篇 |
1982年 | 4篇 |
1981年 | 3篇 |
1979年 | 6篇 |
1977年 | 1篇 |
1976年 | 1篇 |
1975年 | 2篇 |
1973年 | 2篇 |
1972年 | 1篇 |
排序方式: 共有7129条查询结果,搜索用时 9 毫秒
1.
《Molecular & cellular proteomics : MCP》2020,19(7):1161-1178
Highlights
- •XL-MS reveals new PPIs in yeast mitochondria under glycerol and glucose condition.
- •Significant but limited results from quantitative XL-MS experiments.
- •Ndi1 participates in a CIII2CIV2 respiratory supercomplex.
- •Min8 promotes assembly of Cox12 into an intermediate complex IV.
2.
《Cell》2021,184(22):5670-5685.e23
3.
Hyun I. Park 《Analytical biochemistry》2010,396(2):262-60
Matrix metalloproteinases (MMPs) are a family of hydrolytic enzymes that play significant roles in development, morphogenesis, inflammation, and cancer invasion. Endometase (matrilysin 2 or MMP-26) is a putative early biomarker for human carcinomas. The effects of the ionic and nonionic detergents on catalytic activity of endometase were investigated. The hydrolytic activity of endometase was detergent concentration dependent, exhibiting a bell-shaped curve with its maximum activity near the critical micelle concentration (CMC) of nonionic detergents tested. The effect of Brij-35 on human gelatinase B (MMP-9), matrilysin (MMP-7), and membrane-type 1 MMP (MT1-MMP) was further explored. Their maximum catalysis was observed near the CMC of Brij-35 (∼ 90 μM). Their IC50 values were above the CMC. The inhibition mechanism of MMP-7, MMP-9, and MT1-MMP by Brij-35 was a mixed type as determined by Dixon’s plot; however, the inhibition mechanism of endometase was noncompetitive with a Ki value of 240 μM. The catalytic activities of MMPs are influenced by detergents. Monomer of detergents may activate and stabilize MMPs to enhance catalysis, but micelle of detergents may sequester enzyme and block the substrate binding site to impede catalysis. Under physiological conditions, a lipid or membrane microenvironment may regulate enzymatic activity. 相似文献
4.
《Bioorganic & medicinal chemistry》2016,24(18):4444-4451
Nowadays, AT1 receptor (AT1R) antagonists (ARBs) constitute the one of the most prevalent classes of antihypertensive drugs that modulate the renin-angiotensin system (RAS). Their main uses include also treatment of diabetic nephropathy (kidney damage due to diabetes) and congestive heart failure. Towards this direction, our study has been focused on the discovery of novel agents bearing different scaffolds which may evolve as a new class of AT1 receptor antagonists. To fulfill this aim, a combination of computational approaches and biological assays were implemented. Particularly, a pharmacophore model was established and served as a 3D search query to screen the ChEMBL15 database. The reliability and accuracy of virtual screening results were improved by using molecular docking studies. In total, 4 compounds with completely diverse chemical scaffolds from potential ARBs, were picked and tested for their binding affinity to AT1 receptor. Results revealed high nanomolar to micromolar affinity (IC50) for all the compounds. Especially, compound 4 exhibited a binding affinity of 199 nM. Molecular dynamics simulations were utilized in an effort to provide a molecular basis of their binding to AT1R in accordance to their biological activities. 相似文献
5.
The structure of the tightly bound complex of the globular myosin head with F-actin is the key to understanding important details of the mechanism of how the actin-myosin motor functions. The current notion on this complex is based on the docking of known atomic structures of constituent proteins into low-resolution electron-density maps. The atomic structure of the complex was refined by the molecular mechanics method, which consists in minimizing the energy of molecular interaction and which makes it possible to optimize not only the relative position of protein backbones as rigid bodies, but also the position of side chains on the protein interface. The structure calculated using ICM-Pro software, on the one hand, is close to the model obtained using electron microscopy; on the other hand, it ensures the best calculated interaction energy and accounts for the results of mutagenesis experiments. On the basis of the structure obtained, we can suggest the molecular mechanisms underlying the actin-activated release of ATP hydrolysis products from myosin and the decrease in the affinity of myosin for actin upon binding of nucleotides. 相似文献
6.
Christelle Hély Kelly K. Caylor Peter Dowty Samuel Alleaume Robert J. Swap Hank H. Shugart Christopher O. Justice 《Ecosystems》2007,10(7):1116-1132
Abstract
We present a regional fuel load model (1 km2 spatial resolution) applied in the southern African savanna region. The model is based on a patch-scale production efficiency
model (PEM) scaled up to the regional level using empirical relationships between patch-scale behavior and multi-source remote
sensing data (spatio-temporal variability of vegetation and climatic variables). The model requires the spatial distribution
of woody vegetation cover, which is used to determine separate respiration rates for tree and grass. Net primary production,
grass and tree leaf death, and herbivory are also taken into account in this mechanistic modeling approach. The fuel load
model has been calibrated and validated from independent measurements taken from savanna vegetation in Africa southward from
the equator. A sensitivity analysis on the effect of climate variables (incoming radiation, air temperature, and precipitation)
has been conducted to demonstrate the strong role that water availability has in determining productivity and subsequent fuel
load over the southern African region. The model performance has been tested in four different areas representative of a regional
increasing rainfall gradient—Etosha National Park, Namibia, Mongu and Kasama, Zambia, as well as in Kruger National Park,
South Africa. Within each area, we analyze model output from three different magnitudes of canopy coverage (<5, 30, and 50%).
We find that fuel load ranges predicted by the model are globally in agreement with field measurements for the same year.
High rainfall sustains green herbaceous production late in the dry season and delays tree leaf litter production. Effect of
water on production varies across the rainfall gradient with delayed start of green material production in more arid regions. 相似文献
7.
《Chronobiology international》2013,30(5):715-730
The contribution of the renin–angiotensin–aldosterone system (RAAS) to the development of congestive heart failure (CHF) and hypertension (HT) has long been recognized. Medications that are commonly used in the course of CHF and HT are most often given with morning food for the sake of convenience and therapeutic compliance. However, biological rhythms and their responsiveness to environmental clues such as food intake may noticeably impact the effectiveness of drugs used in the management of cardiovascular disorders. Only sparse information about the effect of feeding schedules on the biology of the RAAS and blood pressure (BP) is presently available. Two studies were designed to explore the chronobiology of renin activity (RA), BP, renal sodium (UNa,fe) and potassium (UK,fe) handling in relation to meal timing in dogs. In a first experiment (Study a), blood and urinary samples for measurement of RA, UNa,fe and UK,fe were drawn from 18 healthy beagle dogs fed a normal-sodium diet at either 07:00, 13:00 or 19:00?h. In a second experiment (Study b), BP was recorded continuously from six healthy, telemetered beagle dogs fed a similar diet at 07:00, or 19:00?h. Data were collected throughout 24-h time periods, and analyzed by means of nonlinear mixed-effects models. Differences between the geometric means of early versus late time after feeding observations were further compared using parametric statistics. In agreement with our previous investigations, the results indicate that RA, UNa,fe, UK,fe, systolic, and diastolic BP oscillate with a circadian periodicity in dogs fed a regular diet at 07:00?h. A cosine model with a fixed 24-h period was found to fit the variations of RA, UK,fe and BP well, whereas cyclic changes in UNa,fe were best characterized by means of a combined cosine and surge model, reflecting a postprandial sodium excretion followed by a monotonous decay. Our data show that feeding time has a marked influence on the chronobiology of the renin cascade, urinary electrolytes, and BP. Introducing a 6- or 12-h delay in the dogs’ feeding schedule caused a shift of similar magnitude (05:06 and 12:32?h for Studies a and b, respectively) in the rhythm of these biomarkers. In all study groups, RA and BP exhibited a marked fall just after food intake. The drop in RA is consistent with sodium and water-induced body fluid expansion, while the reduction of BP could be related to the decreased activity of renin and the secretion of vasodilatory gut peptides. An approximately 1.5-fold (1.2–1.6-fold) change between the average early and late time after feeding observations was found for RA (p?<?0.0001), UNa,fe (p?<?0.01) and UK,fe (p?<?0.05). Postprandial variations in BP, albeit small (ca. 10?mmHg), were statistically significant (p?<?0.01) and supported by the model-based analysis.In conclusion, the timing of food intake appears to be pivotal to the circadian organization of the renin cascade and BP. This synchronizing effect could be mediated by feeding-related signals, such as dietary sodium, capable of entraining circadian oscillators downstream of the master, light–dark-adjusted pacemaker in the suprachiasmatic nucleus. 相似文献
8.
9.
The groundbreaking technologies of induced pluripotency and lineage conversion have generated a genuine opportunity to address fundamental aspects of the diseases that affect the nervous system. These approaches have granted us unrestricted access to the brain and spinal cord of patients and have allowed for the study of disease in the context of human cells, expressing physiological levels of proteins and under each patient's unique genetic constellation. Along with this unprecedented opportunity have come significant challenges, particularly in relation to patient variability, experimental design and data interpretation. Nevertheless, significant progress has been achieved over the past few years both in our ability to create the various neural subtypes that comprise the nervous system and in our efforts to develop cellular models of disease that recapitulate clinical findings identified in patients. In this Review, we present tables listing the various human neural cell types that can be generated and the neurological disease modeling studies that have been reported, describe the current state of the field, highlight important breakthroughs and discuss the next steps and future challenges. 相似文献
10.
E. Golomer P. Dupui H. Monod 《European journal of applied physiology and occupational physiology》1997,76(2):140-144
We investigated the effects of maturation on the dynamic body sways of healthy girls. Prepubertal and postpubertal girls
practising professional physical activities requiring a good ability to maintain equilibrium (acrobats and dancers) were asked
to stand on a free seesaw platform and the results compared to those for untrained age-matched girls. This platform (stabilometer)
allows self-induced body sways. Stabilograms were obtained by a double integration of the angular acceleration from the recordings
of the platform sways made with an accelerometer. Fast Fourier transform processing of stabilograms allowed spectral frequency
analysis. The total spectrum energy and the energies of three frequency bands (0–0.5 Hz, 0.5–2 Hz, 2–20 Hz) were determined.
ANOVA showed that, for all groups of different equilibrium activity and independent of visual input, prepubertal girls had
higher energy values than postpubertal girls in the 0- to 0.5-Hz band whereas the opposite was true for 0.5- to 2-Hz band.
Ballet dancers were more dependent than acrobats on visual inputs for the regulation of their postural control but were less
dependent than untrained girls at both ages. Maturation seemed to shift body sways towards higher frequencies and the utilization
of the cues of postural control was different according to the type of equilibrium activity practised by the subjects.
Accepted: 7 February 1997 相似文献