全文获取类型
收费全文 | 15946篇 |
免费 | 870篇 |
国内免费 | 102篇 |
专业分类
耳鼻咽喉 | 155篇 |
儿科学 | 300篇 |
妇产科学 | 179篇 |
基础医学 | 2206篇 |
口腔科学 | 230篇 |
临床医学 | 1602篇 |
内科学 | 3881篇 |
皮肤病学 | 329篇 |
神经病学 | 1921篇 |
特种医学 | 1085篇 |
外科学 | 2491篇 |
综合类 | 79篇 |
一般理论 | 7篇 |
预防医学 | 638篇 |
眼科学 | 228篇 |
药学 | 789篇 |
中国医学 | 7篇 |
肿瘤学 | 791篇 |
出版年
2023年 | 142篇 |
2022年 | 186篇 |
2021年 | 423篇 |
2020年 | 249篇 |
2019年 | 340篇 |
2018年 | 384篇 |
2017年 | 277篇 |
2016年 | 399篇 |
2015年 | 409篇 |
2014年 | 570篇 |
2013年 | 809篇 |
2012年 | 1252篇 |
2011年 | 1232篇 |
2010年 | 756篇 |
2009年 | 716篇 |
2008年 | 1097篇 |
2007年 | 1105篇 |
2006年 | 1047篇 |
2005年 | 1036篇 |
2004年 | 929篇 |
2003年 | 832篇 |
2002年 | 747篇 |
2001年 | 184篇 |
2000年 | 145篇 |
1999年 | 173篇 |
1998年 | 163篇 |
1997年 | 132篇 |
1996年 | 81篇 |
1995年 | 80篇 |
1994年 | 61篇 |
1993年 | 52篇 |
1992年 | 67篇 |
1991年 | 54篇 |
1990年 | 63篇 |
1989年 | 50篇 |
1988年 | 35篇 |
1987年 | 39篇 |
1986年 | 34篇 |
1985年 | 30篇 |
1984年 | 34篇 |
1983年 | 33篇 |
1982年 | 24篇 |
1980年 | 19篇 |
1979年 | 26篇 |
1978年 | 19篇 |
1977年 | 27篇 |
1975年 | 19篇 |
1974年 | 24篇 |
1973年 | 22篇 |
1972年 | 18篇 |
排序方式: 共有10000条查询结果,搜索用时 0 毫秒
81.
Cation channels,cell volume and the death of an erythrocyte 总被引:8,自引:0,他引:8
Lang F Lang KS Wieder T Myssina S Birka C Lang PA Kaiser S Kempe D Duranton C Huber SM 《Pflügers Archiv : European journal of physiology》2003,447(2):121-125
Similar to a variety of nucleated cells, human erythrocytes activate a non-selective cation channel upon osmotic cell shrinkage. Further stimuli of channel activation include oxidative stress, energy depletion and extracellular removal of Cl–. The channel is permeable to Ca2+ and opening of the channel increases cytosolic [Ca2+]. Intriguing evidence points to a role of this channel in the elimination of erythrocytes by apoptosis. Ca2+ entering through the cation channel stimulates a scramblase, leading to breakdown of cell membrane phosphatidylserine asymmetry, and stimulates Ca2+-sensitive K+ channels, thus leading to KCl loss and (further) cell shrinkage. The breakdown of phosphatidylserine asymmetry is evidenced by annexin binding, a typical feature of apoptotic cells. The effects of osmotic shock, oxidative stress and energy depletion on annexin binding are mimicked by the Ca2+ ionophore ionomycin (1 µM) and blunted in the nominal absence of extracellular Ca2+. Nevertheless, the residual annexin binding points to additional mechanisms involved in the triggering of the scramblase. The exposure of phosphatidylserine at the extracellular face of the cell membrane stimulates phagocytes to engulf the apoptotic erythrocytes. Thus, sustained activation of the cation channels eventually leads to clearance of affected erythrocytes from peripheral blood. Susceptibility to annexin binding is enhanced in several genetic disorders affecting erythrocyte function, such as thalassaemia, sickle-cell disease and glucose-6-phosphate dehydrogenase deficiency. The enhanced vulnerability presumably contributes to the shortened life span of the affected erythrocytes. Beyond their role in the limitation of erythrocyte survival, cation channels may contribute to the triggering of apoptosis in nucleated cells exposed to osmotic shock and/or oxidative stress. 相似文献
82.
Isolated envelope proteins of Newcastle disease virus (NDV) were inserted into the lipid bilayer of artificial vesicles to create a viral envelope-like structure. The structure-containing viral antigens at high density elicited a strong immune response, in contrast to purified viral proteins. The artificial envelopes or immunosomes possessed several advantageous properties when used as vaccines. They elicited a faster response and the immunity lasted longer in animals treated with these vesicles than in controls vaccinated with envelope proteins in combination with traditional adjuvants. A further useful feature of the artificial envelopes is that no inflammatory lesions develop at the site of their injection. 相似文献
83.
Brosens I Gordts S Valkenburg M Puttemans P Campo R Gordts S 《Human reproduction (Oxford, England)》2004,19(8):1689-1692
While the appropriate method for the investigation of female infertility continues to be debated, the timing of the investigation has received less attention. The current approach is time-consuming, and paradoxically may lead to overtreatment as well as undertreatment. Recent findings on fecundity and the conception window in humans have important implications for the timing of the investigation of female infertility. The findings support the view that fertility-oriented intercourse may have a major impact in reducing the time to pregnancy. Procedures for the investigation of female infertility are becoming less invasive and more accurate, while the therapies for infertility are more effective. It is proposed that under appropriate circumstances female infertility should be investigated after 6 months of fertility-oriented intercourse. 相似文献
84.
Cunliffe NA Dove W Gondwe JS Thindwa BD Greensill J Holmes JL Bresee JS Monroe SS Glass RI Broadhead RL Molyneux ME Hart CA 《Journal of medical virology》2002,67(4):563-566
In a 2-year hospital-based study of paediatric gastroenteritis in Blantyre, Malawi, astroviruses were detected by enzyme immunoassay in 15 (1.9%) of 786 inpatients and in 9 (2.3%) of 400 outpatients. Greater disease severity was noted in children coinfected with human immunodeficiency virus (HIV). Six human astrovirus (HAstV) genotypes were identified, including HAstV-1 (25%), HAstV-2 (21%), HAstV-3 (25%), HAstV-4 (13%), HAstV-5 (4%), and HAstV-8 (13%). Although astroviruses are not major causes of gastroenteritis among children admitted to hospital in Blantyre, concomitant HIV infection appears to be a risk factor for increased severity of disease. 相似文献
85.
Weber S Doi K Massiello AL Byerman BP Takagaki M Fukamachi K Donahue A Chapman P Hirschman G Vitale N Smith WA 《ASAIO journal (American Society for Artificial Internal Organs : 1992)》2002,48(6):606-611
The purpose of this study was to evaluate the in vitro responses to preload and afterload of our total artificial heart (TAH), the MagScrew TAH. The TAH consists of two blood pumps and a control logic, developed at the Cleveland Clinic, OH, and the MagScrew actuator and its electronic control system, developed by Foster-Miller Technologies, Inc., Albany, NY. Tests were performed on a mock circulatory loop, using water as a test fluid. Preload sensitivity of the Mag-Screw TAH demonstrated a Frank-Starling response to preload in automatic mode. A peak flow of 10 L/min was obtained, with a left atrial pressure of 13 mm Hg. The relationship between right atrial pressure and left atrial pressure was well balanced when tested with a left bronchial shunt flow of 5% and a range of pulmonary artery and aortic pressures. With respect to afterload response, the left pump showed a relatively low sensitivity, which allowed the pump to maintain perfusion over a wide range of aortic pressures. The right pump, on the other hand, was much more sensitive to pulmonary artery pressure, which provided a measure of protection against pulmonary congestion. The very effective physiologic response of the MagScrew TAH is believed to result from employment of a left master, alternating ejection control logic, high inherent sensitivity of the blood pumps to atrial pressure, a lower effective stroke volume for the right pump, and a scaling of right side motor ejection voltage to 80% of that used for the left side ejection. 相似文献
86.
Carson RG Riek S 《Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale》2001,138(1):71-87
The control of movement is predicated upon a system of constraints of musculoskeletal and neural origin. The focus of the present study was upon the manner in which such constraints are adapted or superseded during the acquisition of motor skill. Individuals participated in five experimental sessions, in which they attempted to produce abduction-adduction movements of the index finger in time with an auditory metronome. During each trial, the metronome frequency was increased in eight steps from an individually determined base frequency. Electromyographic (EMG) activity was recorded from first dorsal interosseous (FDI), first volar interosseous (FVI), flexor digitorum superficialis (FDS), and extensor digitorum communis (EDC) muscles. The movements produced on the final day of acquisition more accurately matched the required profile, and exhibited greater spatial and temporal stability, than those generated during initial performance. In the early stages of skill acquisition, an alternating pattern of activation in FDI and FVI was maintained, even at the highest frequencies. In contrast, as the frequency of movement was increased, activity in FDS and EDC was either tonic or intermittent. As learning proceeded, alterations in recruitment patterns were expressed primarily in the extrinsic muscles (EDC and FDS). These changes took the form of increases in the postural role of these muscles, shifts to phasic patterns of activation, or selective disengagement of these muscles. These findings suggest that there is considerable flexibility in the composition of muscle synergies, which is exploited by individuals during the acquisition of coordination. 相似文献
87.
Wang Q Turlington A Heo S Blanco A Tian J Xie Z Yan B Wan Y 《International journal of molecular medicine》2005,15(4):633-640
Activation of cell surface components has been implicated in the activation of downstream signaling cascade in response to UV irradiation, and yet the identity and the interaction of those components have been scantly documented. Accumulating evidence indicates that caveolae encapsulating caveolins is the location for those interactions. We found in cultured human keratinocytes that UV irradiation induced both caveolin-1 and EGFR phosphorylation. Filipin, a caveolae disruptive agent, inhibited UV-induced caveolin-1 activation. Na+-K+-ATPase catalyzes active transport of Na+ and K+ across plasma membrane of mammalian cells, inactivation of which has recently been shown to be involved in the activation of signal transduction pathways including MAP kinase cascade. We found in this study that UV inactivated Na+-K+-ATPase in time-dependent manner, Na+-K+-ATPase activity started to decrease 5 min post UV irradiation and reduced to 60% of its original activity within 1 h. Pretreatment with Flipin and MMP inhibitor recovered Na+-K+-ATPase activity lost by UV irradiation. ECIS analysis indicated that both EGF treatment and UV irradiation increased membrane electric activity which was inhibited by MMP inhibitor and Filipin. Further study showed that pretreatment of human keratinocytes with MMP inhibitor or Filipin inhibited UV-induced phosphorylation of p38 and JNK, which was however not observed in LnCap cells, a prostate cancer cell line lacking caveolin-1. UV irradiation also induced ectodomain shedding of HB-EGF in a time-dependent manner in keratinocytes. Collectively, we conclude that UV-induced MAP kinase activation is mediated by cell surface receptor activation due to the matrix activity and membrane caveolae function and inactivation of Na+-K+-ATPase. 相似文献
88.
Ferrer I Kapfhammer JP Hindelang C Kemp S Troffer-Charlier N Broccoli V Callyzot N Mooyer P Selhorst J Vreken P Wanders RJ Mandel JL Pujol A 《Human molecular genetics》2005,14(23):3565-3577
ATP-binding cassette (ABC) transporters facilitate unidirectional translocation of chemically diverse substances, ranging from peptides to lipids, across cell or organelle membranes. In peroxisomes, a subfamily of four ABC transporters (ABCD1 to ABCD4) has been related to fatty acid transport, because patients with mutations in ABCD1 (ALD gene) suffer from X-linked adrenoleukodystrophy (X-ALD), a disease characterized by an accumulation of very-long-chain fatty acids (VLCFAs). Inactivation in the mouse of the abcd1 gene leads to a late-onset neurodegenerative condition, comparable to the late-onset form of X-ALD [Pujol, A., Hindelang, C., Callizot, N., Bartsch, U., Schachner, M. and Mandel, J.L. (2002) Late onset neurological phenotype of the X-ALD gene inactivation in mice: a mouse model for adrenomyeloneuropathy. Hum. Mol. Genet., 11, 499-505.]. In the present work, we have generated and characterized a mouse deficient for abcd2, the closest paralog to abcd1. The main pathological feature in abcd2-/- mice is a late-onset cerebellar and sensory ataxia, with loss of cerebellar Purkinje cells and dorsal root ganglia cell degeneration, correlating with accumulation of VLCFAs in the latter cellular population. Axonal degeneration was present in dorsal and ventral columns in spinal cord. We have identified mitochondrial, Golgi and endoplasmic reticulum damage as the underlying pathological mechanism, thus providing evidence of a disturbed organelle cross-talk, which may be at the origin of the pathological cascade. 相似文献
89.
An important mechanism by which vertebrate olfactory sensory neurons rapidly adapt to odorants is feedback modulation of the Ca(2+)-permeable cyclic nucleotide-gated (CNG) transduction channels. Extensive heterologous studies of homomeric CNGA2 channels have led to a molecular model of channel modulation based on the binding of calcium-calmodulin to a site on the cytoplasmic amino terminus of CNGA2. Native rat olfactory CNG channels, however, are heteromeric complexes of three homologous but distinct subunits. Notably, in heteromeric channels, we found no role for CNGA2 in feedback modulation. Instead, an IQ-type calmodulin-binding site on CNGB1b and a similar but previously unidentified site on CNGA4 are necessary and sufficient. These sites seem to confer binding of Ca(2+)-free calmodulin (apocalmodulin), which is then poised to trigger inhibition of native channels in the presence of Ca(2+). 相似文献
90.