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排序方式: 共有579条查询结果,搜索用时 15 毫秒
1.
ZK 91296, a partial agonist at benzodiazepine receptors 总被引:2,自引:0,他引:2
Petersen Erling N. Jensen Leif H. Honoré Tage Braestrup Claus Kehr Wolfgang Stephens David N. Wachtel Helmuth Seidelman Dieter Schmiechen Ralph 《Psychopharmacology》1984,83(3):240-248
ZK 91296 (ethyl 5-benzyloxy-4-methoxymethyl--carboline-3-carboxylate) is a potent and selective ligand for benzodiazepine (BZ) receptors. Biochemical investigations indicate that ZK 91296 may be a partial agonist at BZ receptors. Such partial agonism may explain to some extent why ZK 91296 needs higher BZ receptor occupancy than diazepam for the same effect against chemical convulsants and for behavioural effects. The lack of sedatiye effects, and the very potent inhibition of reflex epilepsy, spontaneous epilepsy and DMCM-induced seizures suggest, furthermore, that ZK 91296 may possess pharmacological selectivity for a particular type of BZ receptor interaction, perhaps including topographic as well as receptor subtype differentiation. 相似文献
2.
Helmuth Adelsberger Nicolas von Beckerath Franz Parzefall Josef Dudel 《Pflügers Archiv : European journal of physiology》1996,431(5):680-689
Single-channel measurements were performed with the aim of constructing a detailed molecular scheme for the reaction between -aminobutyric acid (GABA) and a chloride channel of crayfish deep extensor abdominal muscle (DEAM). GABA was applied in pulses to outside-out patches of muscle membrane, and, based on the dose-response of the peak currents and of their rise times, a linear model with five binding steps has been proposed. Evaluation of the single-channel kinetics indicated at least three open states. Two of them originate most probably from the fully liganded receptor state and are grouped in mixed bursts due to their different life times. The third one appears independently, outside the bursts, and originates from a lower liganded receptor state. Simulations of the dose-responses and the open time distributions with this model led to a set of rate constants which generated relatively optimal fits. 相似文献
3.
The serial reaction time (SRT) task has been frequently used to assess procedural learning of sequences. Patients with Parkinson's disease (PD) have been reported to show deficits on this task, but it is as yet unclear whether this impairment reflects a general sequencing deficit or a deficit in the sequencing of motor-output responses. In order to examine this issue, PD patients and controls were administered an SRT task which allowed the simultaneous and independent assessment of the procedural learning of spatial regularities and the learning of motor-response regularities. PD patients were unimpaired at learning a sequence of spatial locations, but showed a deficit at learning a stimulus-to-motor-response sequence. The results suggest that sequencing impairments in PD are not general, but specific to the type of sequential information inherent in a task. 相似文献
4.
Christopher R Gibson Charles Lin Rominder Singh Cheri M Brown Karen Richards Janice Brunner Kimberly Michel Jennifer Adelsberger Edward Carlini Catherine Boothe-Genthe Conrad Raab Minh Luu Aimee Michael Mona Parikh Patrice Ciecko Raju Subramanian Paul Krolikowski A David Rodrigues Thomas A Baillie Thomas H Rushmore 《Drug metabolism and disposition》2005,33(7):1044-1051
Compound I [3-[5-(4-methanesulfonyl-piperazin-1-ylmethyl)-1H-indol-2-yl]-1H-quinolin-2-one] is a potent inhibitor of human kinase insert domain-containing receptor (KDR kinase), which is under investigation for the treatment of cancer. Bile duct-cannulated male beagle dogs were administered 6 mg/kg compound I q.d. for 14 days. There was an approximately 2.5-fold decrease in the mean plasma area under the curve of I on days 7 and 14 (approximately 11.3 microM . h), relative to day 1 (28.2 microM . h). In the dog, compound I was eliminated by metabolism, with a major pathway being aromatic hydroxylation and subsequent sulfation to form the metabolite M3. Metabolic profiling suggested that the pathway leading to the formation of the sulfated conjugate M3 was induced upon multiple dosing of I. Studies conducted in vitro suggested that CYP1A1/2 was responsible for the formation of the hydroxylated metabolite, which is sulfated to yield M3. Additional studies confirmed induction of CYP1A protein and activity in the livers of dogs treated with I. However, studies in a dog hepatocyte model of induction showed a surprising decrease both in CYP1A mRNA and enzymatic activity in the presence of I, emphasizing the need to consider the results from a variety of in vitro and in vivo studies in deriving an understanding of the metabolic fate of a drug candidate. It is concluded that the autoinduction observed after multiple treatments with compound I occurs since compound I is both an inducer and a substrate for dog CYP1A. 相似文献
5.
A new rotational thrombectomy catheter: System design and first clinical experiences 总被引:3,自引:0,他引:3
Hans-Erich Schmitt M.D. Kurt A. Jäger Augustinus L. Jacob Helmuth Mohr Karl-Heinz Labs Wolfgang Steinbrich 《Cardiovascular and interventional radiology》1999,22(6):504-509
Purpose: To describe a new catheter for the percutaneous mechanical removal of fresh and organized thrombi, and to assess its efficacy
and safety in vitro and in vivo.
Methods: The catheter consists of a coated stainless steel spiral that rotates at 40,000 rpm over a guidewire inside the whole length
of an 8 Fr, single-lumen, polyurethane catheter, driving a dual-blade cutting crown. Abraded occlusion material is sucked
into the catheter head through distal side holes and transported by the spiral into a reservoir at the proximal end. The efficacy
of the device was tested in arterial models and fresh bovine carotid arteries (n = 72). In a clinical pilot study 10 patients (8 women, 2 men; mean age 70.6 ± 10.1 years) with occlusions of the superficial femoral
artery (2–12 cm, mean 5.8 cm), not older than 4 weeks, underwent thrombectomy with the new catheter.
Results: In arterial models and bovine cadaver arteries the catheter completely removed fresh thrombi. Occlusion material of higher
consistency was cut into particles of 100–500 μm and transported outside. Thrombectomy was successful and vessel patency restored
in all 10 patients. The ankle/brachial pressure index significantly (p < 0.0005) increased from 0.41 ± 0.18 before intervention to 0.88 ± 0.15 after 48 hr and to 0.84 ± 0.20 after 3 months. Two reocclusions
occurred within 14 days after the intervention.
Conclusion: Thrombectomy with the new device appears to be feasible and safe in patients with acute and subacute occlusions of the femoropopliteal
artery. 相似文献
6.
A case of radiation-induced sarcoma of the chest wall is reported. Twenty-seven years 11 months after orthovoltage radiotherapy of the right breast a 69-year-old woman developed a radiation-induced osteosarcoma of the right thoracic wall. Initial diagnosis has been T-cell lymphoma of the skin. The right breast was irradiated with tangential fields and a total dose of 40 Gy, 2 Gy/day, 5 days a week. Orthovoltage treatment was performed in two courses of 20 Gy, 3 months apart. The clinical appearance of the secondary sarcoma was a diffuse infiltrated area in the irradiated breast which seemed to be fixed to the chest wall. Magnetic resonance imaging (MRI) demonstrated a mass in the right anterior thoracic wall which destroyed the fourth to the sixth rib. The tumor infiltrated the thoracic wall, including subcutaneous tissue and pericardium, as well as extending into the subphrenic space. Biopsy of the lesion revealed a poorly differentiated osteosarcoma. The patient's general condition precluded surgical or chemotherapeutic intervention; she died due to a cerebral stroke 6 months later. This case fulfilled all criteria for radiation-induced sarcoma, as there was a prior history of radiotherapy, latency period of several years, development of sarcoma within the irradiated field, and histologic confirmation of sarcoma. 相似文献
7.
L. Villa B. Guerra S. Schmoger J. Fischer R. Helmuth Z. Zong A. García-Fernández A. Carattoli 《Antimicrobial agents and chemotherapy》2015,59(10):6597-6600
A Salmonella enterica serovar Corvallis strain was isolated from a wild bird in Germany. This strain carried the IncA/C2 pRH-1238 plasmid. Complete sequencing of the plasmid was performed, identifying the blaNDM-1, blaCMY-16, fosA3, sul1, sul2, strA, strB, aac(6′)-Ib, aadA5, aphA6, tetA(A), mphA, floR, dfrA7, and merA genes, which confer clinically relevant resistance to most of the antimicrobial classes, including β-lactams with carbapenems, fosfomycin, aminoglycosides, co-trimoxazole, tetracyclines, and macrolides. The strain likely originated from the Asiatic region and was transferred to Germany through the Milvus migrans migratory route. 相似文献
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