全文获取类型
收费全文 | 59849篇 |
免费 | 5738篇 |
国内免费 | 22篇 |
出版年
2023年 | 211篇 |
2022年 | 500篇 |
2021年 | 1008篇 |
2020年 | 635篇 |
2019年 | 810篇 |
2018年 | 993篇 |
2017年 | 871篇 |
2016年 | 1482篇 |
2015年 | 2450篇 |
2014年 | 2716篇 |
2013年 | 3171篇 |
2012年 | 4232篇 |
2011年 | 4089篇 |
2010年 | 2596篇 |
2009年 | 2361篇 |
2008年 | 3396篇 |
2007年 | 3444篇 |
2006年 | 3274篇 |
2005年 | 3108篇 |
2004年 | 3047篇 |
2003年 | 2781篇 |
2002年 | 2721篇 |
2001年 | 887篇 |
2000年 | 727篇 |
1999年 | 827篇 |
1998年 | 858篇 |
1997年 | 594篇 |
1996年 | 518篇 |
1995年 | 477篇 |
1994年 | 503篇 |
1993年 | 500篇 |
1992年 | 632篇 |
1991年 | 509篇 |
1990年 | 498篇 |
1989年 | 497篇 |
1988年 | 448篇 |
1987年 | 414篇 |
1986年 | 409篇 |
1985年 | 386篇 |
1984年 | 440篇 |
1983年 | 403篇 |
1982年 | 425篇 |
1981年 | 386篇 |
1980年 | 397篇 |
1979年 | 315篇 |
1978年 | 302篇 |
1977年 | 270篇 |
1976年 | 259篇 |
1974年 | 239篇 |
1973年 | 213篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
51.
The physical mechanism of calcium pump regulation in the heart. 总被引:4,自引:3,他引:1
The Ca-ATPase in the cardiac sarcoplasmic reticulum membrane is regulated by an amphipathic transmembrane protein, phospholamban. We have used time-resolved phosphorescence anisotropy to detect the microsecond rotational dynamics, and thereby the self-association, of the Ca-ATPase as a function of phospholamban phosphorylation and physiologically relevant calcium levels. The phosphorylation of phospholamban increases the rotational mobility of the Ca-ATPase in the sarcoplasmic reticulum bilayer, due to a decrease in large-scale protein association, with a [Ca2+] dependence parallel to that of enzyme activation. These results support a model in which phospholamban phosphorylation or calcium free the enzyme from a kinetically unfavorable associated state. 相似文献
52.
Cathrine Laustrup M?ller Rasmus Kj?bsted Pablo J. Enriori Thomas Elbenhardt Jensen Cecilia Garcia-Rudaz Sara A. Litwak Kirsten Raun J?rgen Wojtaszewski Birgitte Schjellerup Wulff Michael A. Cowley 《PloS one》2016,11(7)
The melanocortin system includes five G-protein coupled receptors (family A) defined as MC1R-MC5R, which are stimulated by endogenous agonists derived from proopiomelanocortin (POMC). The melanocortin system has been intensely studied for its central actions in body weight and energy expenditure regulation, which are mainly mediated by MC4R. The pituitary gland is the source of various POMC-derived hormones released to the circulation, which raises the possibility that there may be actions of the melanocortins on peripheral energy homeostasis. In this study, we examined the molecular signaling pathway involved in α-MSH-stimulated glucose uptake in differentiated L6 myotubes and mouse muscle explants. In order to examine the involvement of AMPK, we investigate α-MSH stimulation in both wild type and AMPK deficient mice. We found that α-MSH significantly induces phosphorylation of TBC1 domain (TBC1D) family member 1 (S237 and T596), which is independent of upstream PKA and AMPK. We find no evidence to support that α-MSH-stimulated glucose uptake involves TBC1D4 phosphorylation (T642 and S704) or GLUT4 translocation. 相似文献
53.
Mingyue Wang Pranab K Mukherjee Jyotsna Chandra Ali Abdul Lattif Thomas S McCormick Mahmoud A Ghannoum 《BMC microbiology》2008,8(1):31
Background
We have previously shown that supernatant from Candida albicans (CA) culture contains a Secretory Interleukin (IL)-12 Inhibitory Factor (CA-SIIF), which inhibits IL-12 production by human monocytes. However, the effect of CA-SIIF on secretion of other cytokines by monocytes is unknown, and detailed characterization of this factor has not been performed. 相似文献54.
55.
56.
F. Fontaine E. Kiefer C. Clément M. Burrus J. L. Druelle 《Trees - Structure and Function》1999,14(2):83-90
In the present work, we described the fate of proventitious epicormic buds on the trunks of 40-year-old Quercus petraea trees and in parallel the vascular trace they produced in the wood. Our results show that small and large individual epicormic
buds can survive as buds for 40 years and that both are composed of a terminal meristem and scales. Meristematic areas are
detected in the scale axils of small buds; in addition to these meristems the large buds also have secondary bud primordia.
The small buds are connected to the pith of the main stem by a unique trace, whereas the large buds are connected by one or
multiple traces. A single trace might imply that the whole bud is still alive and multiple traces might indicate that the
terminal meristem has died. In the latter case, each trace is connected to a secondary bud of the large bud. The buds found
in a cluster are composed of a terminal meristem and scales with axillary meristems in the scale axils. A cluster is connected
to the pith of a stem either by a unique trace when it seems to be the result of partial abscission of an epicormic shoot
or multiple traces when it might have originated from an epicormic bud in which the terminal meristem has died. Whatever the
type of the bud, the vascular trace in the bark is composed of a cambium, secondary xylem and parenchyma cells and the trace
present in the wood had parenchyma cells with vestiges of secondary xylem. Each year, the vascular trace should be produced
in the bark by the cambium of the tree but not by the bud itself. On 40-year-old Q. petraea, we observed a proliferation of epicormic buds and in parallel a multiplication of the number of vascular traces in the trunk,
but the knots caused by the traces of epicormic buds in the wood, either as individuals or in clusters, are minor since their
colours are only slightly darker than those of woody rays and they are less than 2 mm in diameter. The knots will appear when
epicormic buds develop into shoots.
Received: 30 March 1999 / Accepted: 09 June 1999 相似文献
57.
Dysfunctional pulmonary homeostasis and repair, including diseases such as pulmonary fibrosis (PF), chronic obstructive pulmonary disease (COPD), and tumorigenesis have been increasing over the past decade, a fact that heavily implicates environmental influences. Several investigations have suggested that in response to increased transforming growth factor - beta (TGFβ) signaling, the alveolar type II (ATII) epithelial cell undergoes phenotypic changes that may contribute to the complex pathobiology of PF. We have previously demonstrated that increased tissue stiffness associated with PF is a potent extracellular matrix (ECM) signal for epithelial cell activation of TGFβ. The work reported here explores the relationship between tissue stiffness and exposure to environmental stimuli in the activation of TGFβ. We hypothesized that exposure of ATII cells to fine particulate matter (PM2.5) will result in enhanced cell contractility, TGFβ activation, and subsequent changes to ATII cell phenotype. ATII cells were cultured on increasingly stiff substrates with or without addition of PM2.5. Exposure to PM2.5 resulted in increased activation of TGFβ, increased cell contractility, and elongation of ATII cells. Most notably, on 8 kPa substrates, a stiffness greater than normal but less than established fibrotic lung, addition of PM2.5 resulted in increased cortical cell stiffness, enhanced actin staining and cell elongation; a result not seen in the absence of PM2.5. Our work suggests that PM2.5 exposure additionally enhances the existing interaction between ECM stiffness and TGFβ that has been previously reported. Furthermore, we show that this additional enhancement is likely a consequence of intracellular reactive oxygen species (ROS) leading to increased TGFβ signaling events. These results highlight the importance of both the micromechanical and biochemical environment in lung disease initiation and suggest that individuals in early stages of lung remodeling during fibrosis may be more susceptible than healthy individuals when exposed to environmental injury adjuvants. 相似文献
58.
Anna Nilsson Thomas E. Fehniger Lena Gustavsson Malin Andersson Kerstin Kenne Gy?rgy Marko-Varga Per E. Andrén 《PloS one》2010,5(7)
Readouts that define the physiological distributions of drugs in tissues are an unmet challenge and at best imprecise, but are needed in order to understand both the pharmacokinetic and pharmacodynamic properties associated with efficacy. Here we demonstrate that it is feasible to follow the in vivo transport of unlabeled drugs within specific organ and tissue compartments on a platform that applies MALDI imaging mass spectrometry to tissue sections characterized with high definition histology. We have tracked and quantified the distribution of an inhaled reference compound, tiotropium, within the lungs of dosed rats, using systematic point by point MS and MS/MS sampling at 200 µm intervals. By comparing drug ion distribution patterns in adjacent tissue sections, we observed that within 15 min following exposure, tiotropium parent MS ions (mass-to-charge; m/z 392.1) and fragmented daughter MS/MS ions (m/z 170.1 and 152.1) were dispersed in a concentration gradient (80 fmol-5 pmol) away from the central airways into the lung parenchyma and pleura. These drug levels agreed well with amounts detected in lung compartments by chemical extraction. Moreover, the simultaneous global definition of molecular ion signatures localized within 2-D tissue space provides accurate assignment of ion identities within histological landmarks, providing context to dynamic biological processes occurring at sites of drug presence. Our results highlight an important emerging technology allowing specific high resolution identification of unlabeled drugs at sites of in vivo uptake and retention. 相似文献
59.
Thomas Cavalier-Smith 《Biology direct》2010,5(1):7
Background
The transition from prokaryotes to eukaryotes was the most radical change in cell organisation since life began, with the largest ever burst of gene duplication and novelty. According to the coevolutionary theory of eukaryote origins, the fundamental innovations were the concerted origins of the endomembrane system and cytoskeleton, subsequently recruited to form the cell nucleus and coevolving mitotic apparatus, with numerous genetic eukaryotic novelties inevitable consequences of this compartmentation and novel DNA segregation mechanism. Physical and mutational mechanisms of origin of the nucleus are seldom considered beyond the long-standing assumption that it involved wrapping pre-existing endomembranes around chromatin. Discussions on the origin of sex typically overlook its association with protozoan entry into dormant walled cysts and the likely simultaneous coevolutionary, not sequential, origin of mitosis and meiosis. 相似文献60.
J L Giacchino M P Thomas J M Horowitz 《Comparative biochemistry and physiology. A, Comparative physiology》1988,89(1):37-44
1. Post-stimulus time (PST) histograms of rat hippocampal cells were recorded in vivo following single-shock stimulation of the fornix. 2. The PST histograms displayed a series of peaks of decreasing amplitude, similar to damped oscillatory responses previously recorded in cats and rabbits. 3. The effect of increased background activity was investigated by recording histograms with concurrent pulse train stimulation of the contralateral hippocampus. The histograms showed a decreased latency to the onset of the second peak. 4. Damped oscillatory activity seen in the in vivo rat preparation could not be elicited in the in vitro rat slice preparation. Thus species differences cannot account for the absence in slice studies of this type of damped oscillatory activity. 5. We conclude that the level of spontaneous activity is one factor contributing to the genesis of multiple peaks in histograms in the in vivo preparation. 相似文献