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91.
92.
Jiang He Mary Rusckowski Yi Wang Shuping Dou Xinrong Liu Surong Zhang Guozheng Liu Donald J. Hnatowich 《Molecular imaging and biology》2007,9(1):17-23
Objective Pretargeting with radioactivity has significantly improved tumor to normal tissue radioactivity ratios over conventional antibody
imaging in both animal studies and clinical trials. This laboratory is investigating DNA analogues such as phosphorodiamidate
morpholinos (MORFs) for pretargeting using technetium-99m (99mTc) for detection. However, the unique properties of fluorescence activation and quenching combined with oligomers with their
unique properties of hybridization may be particularly useful when used together for pretargeting with optical detection.
The use of linear fluorophore-conjugated oligomer duplexes have been little used in animals, and to our knowledge, have not
previously been considered for pretargeting applications.
Methods A MORF/cDNA pair was selected such that when hybridized, the fluorescence of the Cy5.5-conjugated 25 mer MORF (Cy5.5–MORF25)
is inhibited with a BHQ3-conjugated 18 mer complementary DNA (BHQ3–cDNA18). The short BHQ3–cDNA18 was selected to dissociate
in the presence of a long cMORF25 in the pretargeted tumor, thus releasing the inhibitor from the Cy5.5 emitter. In this manner,
the Cy5.5 fluorescence will be inhibited everywhere but in the target. The dissociation was first examined in vitro by adding the duplex to the cMORF25 both in solution and immobilized on polystyrene microspheres and by surface plasmon resonance
(SPR). Thereafter, biotinylated cMORF25 immobilized on streptavidin polystyrene microspheres were administered intramuscularly
in one thigh of hairless SKH-1 mice as target while an identical weight of the identical microspheres but without the cMORF25
was administered in the contralateral thigh as control. The animals then received IV the Cy5.5–MORF25/BHQ3–cDNA18 duplex or
equal molar dosage of single-chain Cy5.5–MORF25 and were imaged.
Results The SPR studies showed that the immobilized cDNA18 rapidly captured the flowing MORF25 to provide a duplex with a slow dissociation
rate constant. Furthermore, when cMORF25 was next allowed to flow over the now immobilized duplex, the cDNA18 was unable to
prevent dissociation of the heteroduplex and the formation and release of the cMORF25-MORF25 homoduplex. Images of animals
obtained soon after receiving the Cy5.5–MORF25 singlet showed intense whole body fluorescence obscuring the target thigh.
However, only 5 minutes after receiving the Cy5.5–MORF25/BHQ3–cDNA18 duplex, the target thigh was clearly visible along with
only the kidneys.
Conclusions This first study of optical pretargeting provides a proof of concept that oligomer pretargeting found to be useful with radioactivity
detection is applicable with fluorescent detection as well. In addition, our results demonstrate that by using linear oligomers
for optical pretargeting, chain lengths (and base sequences) may be manipulated to provide duplexes with stabilities and fluorescence
inhibition optimized for pretargeting and other in vivo applications of optical imaging. 相似文献
93.
The C fibre reflex of the cat urinary bladder 总被引:5,自引:3,他引:2
94.
Acute management of intracranial hemorrhage in patients receiving thrombolytic therapy: case reports
Intracranial hemorrhage is an uncommon complication of antithrombotic therapy. We present two patients who suffered life-threatening intracranial bleeding as a complication of thrombolytic/anticoagulant treatment. Early diagnosis and treatment appear to be crucial factors for survival. We suggest an approach to perioperative management for intracranial hemorrhage resulting from antithrombotic therapy. 相似文献
95.
It is well known that lung cancer develops frequently in patients with idiopathic interstitial pneumonia (IIP) (9.8-22.8%). We investigated 4 patients who developed lung cancer among the 28 patients with IIP (14.3%) who were admitted to our hospital from June 1981 to March 1989. Many reports have pointed out the clinical features of lung cancer associated with IIP as male sex, old age, heavy smoking, and poor prognosis. Our 4 series were agreed with these clinical features. Lung cancer associated with IIP have been often reported to occur in the lower and peripheral regions of the lung, and honeycomb structures are frequently seen. But we found that lung cancer in IIP could actually occur in both the lower and upper regions of the lung and does not occur only in the honeycomb structures. There was no obvious dominance of any histological type among the tumors. If lung cancer is suspected in a patient with IIP, tumor markers are of some value for diagnosis, but are not sensitive enough to be used alone. 相似文献
96.
97.
We have presented the case of a 32-year-old man who sustained blunt trauma to the chest in a motor vehicle accident. Plain roentgenograms showed a widened mediastinum and pneumomediastinum, and an esophagogram with water-soluble contrast material showed an esophageal laceration at the T-4 level. 相似文献
98.
99.
Allen Cato III Linda E. Gustavson Jiang Qian Tawakol El-Shourbagy Edward A. Kelly 《Epilepsia》1998,39(1):43-47
Summary: Purpose: We wished to determine the effect of renal impairment on the pharmacokinetics and tolerability of the new antiepileptic drug tiagabine (TGB).
Methods: We assessed TGB pharmacokinetics and tolerability in 25 subjects with various degrees of renal function (based on creatinine clearance, n = 4–6 per group) from healthy (group I) to requiring hemodialysis (group V) in a single and multiple dose (every 12h), one-period (groups I-IV) or a single dose, two-period (group V) study (4-mg oral doses of TGB · HCl). Blood samples were collected after the first dose (both periods for group V) and after the last dose on day 5 (groups I-IV). TGB plasma concentrations and plasma protein binding were determined by high-performance liquid chromatography (HPLC) and ultrafiltration, respectively.
Results: TGB was well tolerated by all study subjects. The pharmacokinetics of TGB were similar in all subjects; no pharmacokinetic parameter (based on either total or unbound concentrations) was statistically correlated with creatinine clearance. For total TGB in plasma, single-dose mean values of the maximum plasma concentration, clearance, and half-life (t1/2) ranged from 52 to 108 ng/ml, from 7.14 to 11.02 I/h, and from 6.4 to 8.4 h, respectively.
Conclusions: TGB pharmacokinetics and tolerability were independent of renal function; therefore, dosage adjustment is unnecessary for epilepsy patients with renal impairment. 相似文献
Methods: We assessed TGB pharmacokinetics and tolerability in 25 subjects with various degrees of renal function (based on creatinine clearance, n = 4–6 per group) from healthy (group I) to requiring hemodialysis (group V) in a single and multiple dose (every 12h), one-period (groups I-IV) or a single dose, two-period (group V) study (4-mg oral doses of TGB · HCl). Blood samples were collected after the first dose (both periods for group V) and after the last dose on day 5 (groups I-IV). TGB plasma concentrations and plasma protein binding were determined by high-performance liquid chromatography (HPLC) and ultrafiltration, respectively.
Results: TGB was well tolerated by all study subjects. The pharmacokinetics of TGB were similar in all subjects; no pharmacokinetic parameter (based on either total or unbound concentrations) was statistically correlated with creatinine clearance. For total TGB in plasma, single-dose mean values of the maximum plasma concentration, clearance, and half-life (t1/2) ranged from 52 to 108 ng/ml, from 7.14 to 11.02 I/h, and from 6.4 to 8.4 h, respectively.
Conclusions: TGB pharmacokinetics and tolerability were independent of renal function; therefore, dosage adjustment is unnecessary for epilepsy patients with renal impairment. 相似文献
100.
Pharmaceutical Research - 相似文献