全文获取类型
收费全文 | 7561篇 |
免费 | 818篇 |
国内免费 | 2篇 |
专业分类
8381篇 |
出版年
2022年 | 65篇 |
2021年 | 118篇 |
2020年 | 75篇 |
2019年 | 93篇 |
2018年 | 96篇 |
2017年 | 74篇 |
2016年 | 162篇 |
2015年 | 223篇 |
2014年 | 290篇 |
2013年 | 376篇 |
2012年 | 498篇 |
2011年 | 494篇 |
2010年 | 293篇 |
2009年 | 287篇 |
2008年 | 396篇 |
2007年 | 348篇 |
2006年 | 324篇 |
2005年 | 350篇 |
2004年 | 358篇 |
2003年 | 330篇 |
2002年 | 297篇 |
2001年 | 130篇 |
2000年 | 149篇 |
1999年 | 146篇 |
1998年 | 92篇 |
1997年 | 79篇 |
1996年 | 89篇 |
1995年 | 78篇 |
1994年 | 84篇 |
1993年 | 65篇 |
1992年 | 106篇 |
1991年 | 115篇 |
1990年 | 94篇 |
1989年 | 100篇 |
1988年 | 105篇 |
1987年 | 96篇 |
1986年 | 75篇 |
1985年 | 90篇 |
1984年 | 94篇 |
1983年 | 74篇 |
1982年 | 52篇 |
1980年 | 49篇 |
1979年 | 58篇 |
1978年 | 57篇 |
1977年 | 56篇 |
1976年 | 46篇 |
1975年 | 50篇 |
1974年 | 76篇 |
1973年 | 61篇 |
1972年 | 43篇 |
排序方式: 共有8381条查询结果,搜索用时 9 毫秒
91.
92.
Previous spaceflight reports attribute changes in plant ultrastructure to microgravity, but it was thought that the changes might result from growth in uncontrolled environments during spaceflight. To test this possibility, potato explants were examined (a leaf, axillary bud, and small stem segment) grown in the ASTROCULTURETM plant growth unit, which provided a controlled environment. During the 16 d flight of space shuttle Columbia (STS-73), the axillary bud of each explant developed into a mature tuber. Upon return to Earth, tuber slices were examined by transmission electron microscopy. Results showed that the cell ultrastructure of flight-grown tubers could not be distinguished from that of tuber cells grown in the same growth unit on the ground. No differences were observed in cellular features such as protein crystals, plastids with starch grains, mitochondria, rough ER, or plasmodesmata. Cell wall structure, including underlying microtubules, was typical of ground-grown plants. Because cell walls of tubers formed in space were not required to provide support against the force due to gravity, it was hypothesized that these walls might exhibit differences in wall components as compared with walls formed in Earth-grown tubers. Wall components were immunolocalized at the TEM level using monoclonal antibodies JIM 5 and JIM 7, which recognize epitopes of pectins, molecules thought to contribute to wall rigidity and cell adhesion. No difference in presence, abundance or distribution of these pectin epitopes was seen between space- and Earth-grown tubers. This evidence indicates that for the parameters studied, microgravity does not affect the cellular structure of plants grown under controlled environmental conditions. 相似文献
93.
Stark JH Sharma R Ostroff S Cummings DA Ermentrout B Stebbins S Burke DS Wisniewski SR 《PloS one》2012,7(3):e34245
Background
Influenza is a contagious respiratory disease responsible for annual seasonal epidemics in temperate climates. An understanding of how influenza spreads geographically and temporally within regions could result in improved public health prevention programs. The purpose of this study was to summarize the spatial and temporal spread of influenza using data obtained from the Pennsylvania Department of Health''s influenza surveillance system.Methodology and Findings
We evaluated the spatial and temporal patterns of laboratory-confirmed influenza cases in Pennsylvania, United States from six influenza seasons (2003–2009). Using a test of spatial autocorrelation, local clusters of elevated risk were identified in the South Central region of the state. Multivariable logistic regression indicated that lower monthly precipitation levels during the influenza season (OR = 0.52, 95% CI: 0.28, 0.94), fewer residents over age 64 (OR = 0.27, 95% CI: 0.10, 0.73) and fewer residents with more than a high school education (OR = 0.76, 95% CI: 0.61, 0.95) were significantly associated with membership in this cluster. In addition, time series analysis revealed a temporal lag in the peak timing of the influenza B epidemic compared to the influenza A epidemic.Conclusions
These findings illustrate a distinct spatial cluster of cases in the South Central region of Pennsylvania. Further examination of the regional transmission dynamics within these clusters may be useful in planning public health influenza prevention programs. 相似文献94.
Local and global cerebral blood flow and glucose utilization in the α-galactosidase A knockout mouse model of Fabry disease 总被引:2,自引:0,他引:2
Yoshiaki Itoh Takanori Esaki Michelle Cook Pankaj Qasba † Kazuaki Shimoji § Joseph Alroy ‡ Roscoe O. Brady † Louis Sokoloff David F. Moore† 《Journal of neurochemistry》2001,79(6):1217-1224
Fabry disease is an X-linked lysosomal disorder characterized by deficient alpha-galactosidase A activity and intracellular accumulations of glycosphingolipids, mainly globotriaosylceramide (Gb3). Clinically, patients occasionally present CNS dysfunction. To examine the pathophysiology underlying brain dysfunction, we examined glucose utilization (CMR(glc)) and cerebral blood flow (CBF) globally and locally in 18 brain structures in the alpha-galactosidase A gene knockout mouse. Global CMR(glc) was statistically significantly reduced by 22% in Fabry mice (p < 0.01). All 18 structures showed decreases in local CMR(glc) ranging from 14% to 33%. The decreases in all structures of the diencephalon, caudate-putamen, brain stem, and cerebellar cortex were statistically significant (p < 0.05). Global cerebral blood flow (CBF) and local CBF measured in the same 18 structures were lower in Fabry mice than in control mice, but none statistically significantly. Histological examination of brain revealed no cerebral infarcts but abundant Gb3 deposits in the walls of the cerebral vessels with neuronal deposits localized to the medulla oblongata. These results indicate an impairment in cerebral energy metabolism in the Fabry mice, but one not necessarily due to circulatory insufficiency. 相似文献
95.
96.
Dimerization and phosphorylation of thyrotropin-releasing hormone (TRH) receptors was characterized using HEK293 and pituitary GHFT cells expressing epitope-tagged receptors. TRH receptors tagged with FLAG and hemagglutinin epitopes were co-precipitated only if they were co-expressed, and 10-30% of receptors were isolated as hemagglutinin/FLAG-receptor dimers under basal conditions. The abundance of receptor dimers was increased when cells had been stimulated by TRH, indicating that TRH either stabilizes pre-existing dimers or increases dimer formation. TRH increased receptor dimerization and phosphorylation within 1 min in a dose-dependent manner. TRH increased phosphorylation of both receptor monomers and dimers, documented by incorporation of (32)P and an upshift in receptor mobility reversed by phosphatase treatment. The ability of TRH to increase receptor phosphorylation and dimerization did not depend on signal transduction, because it was not inhibited by the phospholipase C inhibitor. Receptor phosphorylation required an agonist but was not blocked by the casein kinase II inhibitor apigenin, the protein kinase C inhibitor GF109203X, or expression of a dominant negative form of G protein-coupled receptor kinase 2. TRH receptors lacking most of the cytoplasmic carboxyl terminus formed dimers constitutively but failed to undergo agonist-induced dimerization and phosphorylation. TRH also increased phosphorylation and dimerization of TRH receptors expressed in GHFT pre-lactotroph cells. 相似文献
97.
Douglas W.P. Hay Roseanna M. Muccitelli Derek L. Hortsmeyer David Raeburn 《Prostaglandins & other lipid mediators》1988,35(4)
To examine further the possible prostanoid involvement in the influence of the epithelium on guinea-pig tracheal smooth muscle responsiveness, we have analyzed the effects of LTD4, methacholine and histamine on the level of airway smooth muscle tone and on the amounts of PGE2α and PGI2 (determined by radioimmunoassay) in the presence and absence of the epithelium. Removal of the epithelium increased the sensitivity of guinea-pig trachea to the contractile effects of LTD4, methacholine and histamine. LTD4 (3–100 nM), methacoline (0.1–10 μM) or histamine (0.3–30 μM) did not increase prostanoid release above control values in either the presence or absence of the epithelium. The unstimulated release of PGE2 and PGF2α but not PGI2, was decreased in tissues lacking epithelium. Indomethacin (1 μM) reduced the baseline tone to a smaller extent in the absence of epithelium. In the presence but not the absence of the epithelium, indomethacin increased the sensitivity of preparations to the contractile effect of methacholine. The results support the postulate of an epithelium-derived inhibitory factor modulating guinea-pig tracheal smooth muscle responsiveness. The identity of this factor is not known but is not PGI2 and is unlikely to be PGF2α or PGE2. However, the possibility remains that the basal release of PGE2 and/or PGF2α derived from the epithelium may markedly affect the responsiveness of guinea-pig tracheal smooth muscle. Furthermore, the epithelium is a significant source of PGE2 and PGF2α which may be involved in the maintenance of baseline tone. 相似文献
98.
Salmonella typhimurium AhpC is a founding member of the peroxiredoxin family, a ubiquitous group of cysteine-based peroxidases with high reactivity toward hydrogen peroxide, organic hydroperoxides, and peroxynitrite. For all of the peroxiredoxins, the catalytic cysteine, referred to as the peroxidatic cysteine (C(P)), acts as a nucleophile in attacking the peroxide substrate, forming a cysteine sulfenic acid at the active site. Because thiolates are far stronger nucleophiles than thiol groups, it is generally accepted that cysteine-based peroxidases should exhibit pK(a) values lower than an unperturbed value of 8.3-8.5. In this investigation, several independent approaches were used to assess the pK(a) of the two cysteinyl residues of AhpC. Methods using two different iodoacetamide derivatives yielded unperturbed pK(a) values (7.9-8.7) for both cysteines, apparently due to reactivity with the wrong conformation of C(P) (i.e., locally unfolded and flipped out of the active site), as supported by X-ray crystallographic analyses. A functional pK(a) of 5.94 +/- 0.10 presumably reflecting the titration of C(P) within the fully folded active site was obtained by measuring AhpC competition with horseradish peroxidase for hydrogen peroxide; this value is quite similar to that obtained by analyzing the pH dependence of the epsilon(240) of wild-type AhpC (5.84 +/- 0.02) and similar to those obtained for two typical 2-cysteine peroxiredoxins from Saccharomyces cerevisiae (5.4 and 6.0). Thus, the pK(a) value of AhpC balances the need for a deprotonated thiol (at pH 7, approximately 90% of the C(P) would be deprotonated) with the fact that thiolates with higher pK(a) values are stronger nucleophiles. 相似文献
99.
Summary Cell plate formation inChara zeylanica was compared with recent models of cytokinesis in higher plants in order to gain insight into the evolutionary origin of plant cytokinetic processes. Transmission electron microscopy (TEM) reveals that while cytokinesis inC. zeylanica bears many features in common with that in higher plants, there are significant differences. Unlike that in higher plants, cytokinesis inC. zeylanica begins with a congregation of smooth membrane tubules that are closely associated with endoplasmic reticulum (ER) and Golgi membranes. Mitochondria and other organelles excluded by the phragmoplast in higher plants are present as well. Unlike in higher plants, phragmoplast microtubules persist throughout cytokinesis inC. zeylanica, and the cell plate generally forms across the whole cell at once, though development is patchy, due to small regions developing at different rates; the ends of the plate form last. By identifying aspects of cytokinesis that are different inC. zeylanica and plants, our study indicates which cytokinetic features are more likely to be derived, and which are more likely to be ancestral. In addition, we demonstrated that all nodal cells ofC. zeylanica are interconnected via plasmodesmata, lending support to the idea that, whileChara spp. are generally considered to be filamentous organisms, nodal regions may be thought of as meristemlike tissues.Abbreviations HPF
high-pressure freezing
- KFe
potassium ferricyanide
- SCF
stepwise chemical fixation
- TEM
transmission electron microscopy 相似文献
100.
De Jonghe BC Hayes MR Banno R Skibicka KP Zimmer DJ Bowen KA Leichner TM Alhadeff AL Kanoski SE Cyr NE Nillni EA Grill HJ Bence KK 《American journal of physiology. Endocrinology and metabolism》2011,300(6):E1002-E1011
The adipose tissue-derived hormone leptin regulates energy balance through catabolic effects on central circuits, including proopiomelanocortin (POMC) neurons. Leptin activation of POMC neurons increases thermogenesis and locomotor activity. Protein tyrosine phosphatase 1B (PTP1B) is an important negative regulator of leptin signaling. POMC neuron-specific deletion of PTP1B in mice results in reduced high-fat diet-induced body weight and adiposity gain due to increased energy expenditure and greater leptin sensitivity. Mice lacking the leptin gene (ob/ob mice) are hypothermic and cold intolerant, whereas leptin delivery to ob/ob mice induces thermogenesis via increased sympathetic activity to brown adipose tissue (BAT). Here, we examined whether POMC PTP1B mediates the thermoregulatory response of CNS leptin signaling by evaluating food intake, body weight, core temperature (T(C)), and spontaneous physical activity (SPA) in response to either exogenous leptin or 4-day cold exposure (4°C) in male POMC-Ptp1b-deficient mice compared with wild-type controls. POMC-Ptp1b(-/-) mice were hypersensitive to leptin-induced food intake and body weight suppression compared with wild types, yet they displayed similar leptin-induced increases in T(C). Interestingly, POMC-Ptp1b(-/-) mice had increased BAT weight and elevated plasma triiodothyronine (T(3)) levels in response to a 4-day cold challenge, as well as reduced SPA 24 h after cold exposure, relative to controls. These data show that PTP1B in POMC neurons plays a role in short-term cold-induced reduction of SPA and may influence cold-induced thermogenesis via enhanced activation of the thyroid axis. 相似文献