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101.
102.
Kirton CM Laukkanen ML Nieminen A Merinen M Stolen CM Armour K Smith DJ Salmi M Jalkanen S Clark MR 《European journal of immunology》2005,35(11):3119-3130
Human vascular adhesion protein-1 (VAP-1) is a homodimeric 170-kDa sialoglycoprotein that is expressed on the surface of endothelial cells and functions as a semicarbazide-sensitive amine oxidase and as an adhesion molecule. Blockade of VAP-1 has been shown to reduce leukocyte adhesion and transmigration in in vivo and in vitro models, suggesting that VAP-1 is a potential target for anti-inflammatory therapy. In this study we have constructed mouse-human chimeric antibodies by genetic engineering in order to circumvent the potential problems involved in using murine antibodies in man. Our chimeric anti-VAP-1 antibodies, which were designed to lack Fc-dependent effector functions, bound specifically to cell surface-expressed recombinant human VAP-1 and recognized VAP-1 in different cell types in tonsil. Furthermore, the chimeric antibodies prevented leukocyte adhesion and transmigration in vitro and in vivo. Hence, these chimeric antibodies have the potential to be used as a new anti-inflammatory therapy. 相似文献
103.
Patrick Gonzalez De La Fuente Jean -Pierre Savineau Roger Marthan 《Pflügers Archiv : European journal of physiology》1995,429(5):617-624
The effect of thapsigargin (TG) and cyclopiazonic acid (CPA) on the mechanical activity of the rat pulmonary artery were investigated. In chemically (-escin)-skinned arterial strips, application of TG (0.1–1 M) or CPA (0.5–10 M) prior and throughout the loading procedure of the internal Ca2+ stores (0.3 M free Ca2+ ions for 8–10 min) concentration dependently inhibited the subsequent contractile response induced by noradrenaline (NA, 10 M) or caffeine (25 mM). In intact strips repeatedly incubated in a Ca2+-containing solution (2.5 mM for 10 min), followed by incubation in a Ca2+-free solution 12 min before NA-stimulation, TG and CPA not only inhibited the NA-induced contraction but also increased the tension which appeared during the exposure time to Ca2+. The two phenomena developed with similar time courses. The increase in tension during the readmission of Ca2+ ions was not antagonized by verapamil (10 M) or nifedipine (1 M) but was blocked by La3+ (50 M) and Co2+ (1 mM) ions. The amplitude of the verapamil-insensitive TG (or CPA)-induced contraction was dependent on the external [Ca2+] [0.1–10 mM, concentration for half maximal effect (EC50) =0.85 mM], not modified by the reduction of the external [Na+] (from 130 to 10 mM) and decreased by depolarization of the strip using K+-rich (30–120 mM) solutions. Under the latter condition, 38±9 and 83±4% reduction (n=5) was observed in the presence of 60 and 120 mM K+ respectively. This contraction was also concentration dependently inhibited by the tyrosine kinase inhibitors genistein (0.5–50 M) and tyrphostin (2–50 M). Sr2+ ions, which contracted both depolarized intact and skinned strips, failed to replace Ca2+ ions in the verapamil-insensitive contraction induced by TG or CPA (n=4). Finally, TG (1 M) and CPA (10 M) did not modify the pCa tension relationship in skinned strips (n=5). These results show that the main action of TG and CPA in rat pulmonary artery is to prevent the refilling of the internal Ca2+ store. TG and CPA also seem to facilitate a Ca2+ influx through a specific verapamil-insensitive pathway. The biophysical and molecular characteristics of this pathway remain to be elucitated, although it appears to involve a tyrosine kinase activity. 相似文献
104.
Peter Sandner Bernhard Gess Konrad Wolf Armin Kurtz 《Pflügers Archiv : European journal of physiology》1996,431(6):905-912
There is accumulating evidence from in vitro experiments that the gene expression of the vascular endothelial growth factor
(VEGF) is, like that of the erythropoietin (EPO) gene, regulated by the oxygen tension and by divalent cations such as cobalt.
Since the information about the regulation of VEGF gene expression in vivo is rather scarce, this study aimed to examine the
influence of hypoxia and of cobalt on VEGF gene expression in different rat organs and to compare it with that on EPO gene
expression. To this end male Sprague-Dawley rats were exposed to carbon monoxide (0.1% CO), hypoxia (8% O2 ) or to cobalt chloride (12 and 60 mg/kg s.c.) for 6 h. mRNA levels for VEGF- 188, -164, and -120 amino acid isoforms in
lungs, hearts, kidneys and livers were semiquantitated by RNase protection. For these organs we found a rank order of VEGF
mRNA abundance of lung >> heart > kidney = liver. EPO mRNA levels were semiquantitated in kidneys and livers. Hypoxia, CO
and cobalt increased EPO mRNA levels 60-fold, 140-fold and 5-fold, respectively, in the kidneys, and 11-fold, 11-fold and
3-fold, respectively, in the livers. None of these manoeuvres caused significant changes of VEGF mRNA in lung, heart or kidneys.
Only in the livers did hypoxia lead to a significant (50%) increase of VEGF mRNA. These findings suggest that, in contrast
to the in vitro situation, the expression of the VEGF gene in normal rat tissues is rather insensitive to hypoxia. In consequence,
the in vivo regulation of the VEGF and the EPO genes appear to differ substantially, suggesting that the regulation of the
VEGF and EPO genes may not follow the same essential mechanisms in vivo.
Received: 31 July 1995/Received after revision: 20 November 1995/Accepted: 27 November 1995 相似文献
105.
Enzymatically dispersed smooth muscle cells of the guinea-pig portal vein were studied by the patch-clamp technique. They were found to have Ca2+-dependent K+ channels with the typical properties of the BK channel, i.e. a reversal potential at the calculated equilibrium potential for K+ ions, a striking voltage dependence, and a conductance of approximately 200 pS ([K+]0 50 mM, [K+]i 150 mM, positive patch potentials). Tedisamil, a new bradycardic agent with an inhibitory action on K+ currents in heart muscle, reduced the open probability of the BK channels concentration-dependently (1–100 M) when applied at the cytosolic side of membrane inside-out patches. At 100 M [Ca2+]i, the IC50 of tedisamil was 13.8 M (¯x, n=5). Tedisamil increased the frequency of channel closures, and reduced the mean duration of openings from 8 ms to < 1 ms, while the mean duration of closures within bursts (1–2 ms) was not altered. Tedisamil did not affect long closures (> 160 ms) between bursts, either. The mean time of residence of tedisamil at the BK channel was estimated to be 1–2ms. Hence, tedisamil, in comparison to the slow blocker Ba2+ and the fast blocker tetraethylammonium, holds the position of an intermediate K+ channel blocker.Supported by the Deutsche Forschungsgemeinschaft 相似文献
106.
纤维蛋白原与吸附白蛋白、肝素的新型血管支架材料氧化钛的血液相容性 总被引:10,自引:0,他引:10
探索纤维蛋白原(Fibrinogen,FIG)与吸附白蛋白、肝素的新型血管支架材料氧化钛(Titanium Oxide,Ti-O)的血液相容性。(1)研制Ti-O,切割成薄膜;(2)Ti-O薄膜涂层白蛋白和肝素;(3)血小板(platelet,PL)吸附试验;(4)酶联免疫试验测FIG吸附量;(5)动物犬股动脉内植入涂层的Ti-O薄膜与对照试片Ti-O和不锈钢(Stainless steel,SS)薄膜。结果发现:Ti-O完全具有固定白蛋白和肝素的结构与性能,比未涂层的Ti-O能更一步减少PL和FIG的吸附,实验动物体内薄膜6个月后取出扫描电镜观察黏附的PL少,形态无改变,血管内无血栓,优于未涂层的Ti-O,更明显优于SS。Ti-O为N型半导体,不易接受FIG的电荷,并且与血细胞有相似的界面张力,决定生物材料Ti-O有较好的血液相容性。Ti-O对白蛋白、肝素有极好的亲和力是因以化学键相结合,在血中进一步减少FIG和PL被涂层的Ti-O吸附。实验证明涂层的Ti-O有持久和稳定的抗凝血性能。 相似文献
107.
108.
Autoregulatory adjustments in the caliber of cerebral arterioles were studied in anesthetized cats equipped with cranial windows
for the direct observation of the pial microcirculation. Increased venous pressure caused slight, but consistent, arteriolar
dilation, at normal and at reduced arterial blood pressure and irrespective of whether or not intracranial pressure was kept
constant or allowed to increase. Arterial hypotension caused arteriolar dilation which was inhibited partially by perfusion
of the space under the cranial window with artificial CSF equilibrated with high concentrations of oxygen. This vasodilation
was inhibited to a greater extent by perfusion of the space under the cranial window with fluorocarbon FC-80, equilibrated
with high concentrations of oxygen. CSF or fluorocarbon equilibrated with nitrogen did not influence the vasodilation in response
to arterial hypotension. The response to increased venous pressure was converted to vasoconstriction when fluorocarbon equilibrated
with high concentrations of oxygen was flowing under the cranial window. The vasodilation in response to arterial hypotension
was inhibited by topical application of adenosine deaminase. The results show that both metabolic and myogenic mechanisms
play a role in cerebral arteriolar autoregulation. Under normal conditions, the metabolic mechanisms predominate. The presence
of the myogenic mechanisms may be unmasked by preventing the operation of the metabolic mechanisms. The major metabolic mechanism
seems to be dependent on changes in PO2 within the brain with secondary release of adenosine. 相似文献
109.
Dynamic graciloplasty has recently been developed for reconstruction of anal function in patients who are fecally incontinent in preference to permanent abdominal colostomy. Since the muscular portion of gracilis is wrapped around the neoanus, the length of the gracilis arc influences the functional outcome of graciloplasty. Although dissection of the main pedicle (i.e. the main artery and vein) can facilitate gracilis to have enough muscle arc, it has been unclear whether there are any vessels proximal to the main pedicle or through the origin of the muscle which could support blood flow into the whole of gracilis. In this study, the vascular anatomy of gracilis in both legs of 26 Japanese cadavers was examined. All muscles had a main pedicle, mean maximum diameter 1.08 mm, entering at the proximal one-third of the muscle. However, only 18 muscles (34.6%) had an accessory artery in the proximal portion in addition to the main pedicle. Some arteries always exist at the origin of the muscle, having a mean maximum diameter of 0.34 mm, suggesting that they might be able to support the whole gracilis without supply from the main pedicle. 相似文献
110.
A fourth case of ring chromosome 7 总被引:1,自引:0,他引:1
An 8-year-old child with a ring chromosome 7 is presented, the first female and the fourth such individual to be described. The associated anomalies were rather benign: she presented with short stature, minor skeletal alterations, and normal intelligence. The only truly striking feature was the presence of multiple large, pigmented naevi, suggestive of a hamartomatous origin, but unlike those typical of any particular syndrome. Though other ring 7 patients have had naevus flammeus, and one had cafk-au-lait spots, our proband is the first with an anomaly of chromosome 7 to have such extensive lesions. These four cases of ring 7, which show great phenotypic variation, are reviewed, and the clinical presentation of the proband is also compared with that of patients suffering from terminal, interstitial and translocation-derived 7p and 7q deletions. The formation and behaviour of ring chromosomes are discussed, as are the cytogenetic factors which may influence their phenotypic expression. 相似文献